Cell Bio Lecture 1 READINGS:

Chapter 10: Despite their fluidity, lipid bilayers can form domains of different compositions

- Because a lipid bilayer is a two-dimensional fluid, we might expect most types of lipid molecules in it to be well mixed and randomly distributed in their own monolayer. The van der Waals attractive forces between neighboring hydrocarbon tails are not selective enough to hold groups of phospholipid molecules together. With certain lipid mixtures in artificial bilayers, however, one can observe phase segregations in which specific lipids come together in separate domains -There has been a long debate among cell biologists about whether the lipid molecules in the plasma membrane of living cells similarly segregate into spe- cialized domains, called lipid rafts. Although many lipids and membrane pro- teins are not distributed uniformly, large-scale lipid phase segregations are rarely seen in living cell membranes. -Instead, specific membrane proteins and lipids are seen to concentrate in a more temporary, dynamic fashion facilitated by protein- protein interactions that allow the transient formation of specialized membrane regions (Figure 10-13). Such clusters can be tiny nanoclusters on a scale of a few molecules, or larger assemblies that can be seen with electron microscopy, such as the caveolae involved in endocytosis -The tendency of mixtures of lipids to undergo phase partitioning, as seen in artificial bilayers (see Figure 10-12), may help create rafts in living cell membranes—organizing and concentrating membrane proteins either for transport in membrane vesicles or for working together in protein assemblies, such as when they convert extracellular signals into intracellular ones ------ Figure 10-13 a model of a raft domain. Weak protein-protein, protein-lipid, and lipid-lipid interactions reinforce one another to partition the interacting components into raft domains. cholesterol, sphingolipids, glycolipids, glycosylphosphatidylinositol (gpI)-anchored proteins, and some transmembrane proteins are enrichedin these domains. note that because of their composition, raft domains have an increased membrane thickness.We discuss glycolipids, gpI-anchored proteins, and oligosaccharide linkers later

Organelles: Endosomes

- On the way to lysosomes, ENDOCYTOSED material must first pass through a series of organelles called ENDOSOMES - membrane-found vesicles, formed via a complex family of processes collectively known as ENDOCYTOSIS, and found in the cytoplasm of virtually every animal cell

Signal Sequences and Sorting Receptors Direct Proteins to the Correct Cell Address:

- most protein sorting signals involved in transmembrane transport reside in a stretch of amino acid sequence, typically 15-60 residues long. - such SIGNAL SEQUENCES are often found at the N terminus of the polypeptide chain, and in many cases specialized SIGNAL PEPTIDASES remove the signal sequence from the finished protein once the sporting process is complete - signal sequences can also be internal stretches of amino acids which remain part of the protein; such signals are used in gated transport into the nucleus > sorting signals can also be made of multiple internal amino acid sequences that form a specific 3-D arrangement of atoms on the protein's surface; such SIGNAL PATCHES are sometimes used for nuclear import and in vesicular transport ----- - each signal sequence specified a particular destination in the cell; proteins destined for initial transfer to the ER usually have a signal sequence at their N-terminus that characteristically includes a sequence composed of about 5-10 hydrophobic amino acids; many of these proteins will in turn pass from the ER to the Golgi apparatus, **but those w/ a specific signal sequence of four amino acids at their C-terminus are recognized as ER residents and are returned to the ER.** --- placing the N-terminal ER signal sequence at the beginning of a cytosolic protein, eg) redirects the protein to the ER; removing or mutating the signal sequence of an ER protein causes its retention in the cytosol. --- proteins destined for mitochondria have signal sequences of yet another type, in which positively charged amino acid alternate w/hydrophobic ones. --- many proteins destined for peroxisomes have a signal sequence of three characteristic amino acids at their C-terminius --- signal sequences are therefore both necessary & sufficient for protein targeting; even tho their amino acid sequences can vary greatly, the signal sequences of proteins have the same destination are functionally interchangeable; physical properties such as hydrophobicity, often seem to be MORE important in the signal-recognition process than the exact amino acid sequence. --- signal sequences are recognized by complementary sorting receptors that guide proteins to their appropriate destination, where the receptors unload their cargo. The receptors function CATALYTICALLY: after completing one round of targeting, they return to their point of origin to be reused. -- Most sorting receptors recognize classes of proteins rather than an individual protein species; they can therefore be viewed as public transportation systems; dedicated to the delivering numerous different components to their correct location in the cell. -- +H3N indicates the N-terminus of a protein; COO- indicates the C-terminus

Organelle: Golgi Apparatus

- the ER sends many of its proteins & lipids to the Golgi apparatus, which often consists of organized stacks of disc-like compartments called Golgi cisternae; -the Golgi apparatus receives lipids and & proteins from the ER and dispatches them to various destinations, usually covalently modifying them EN ROUTE

Chapter 10: The Fluidity of a Lipid Bilayer Depends on its Composition

- the fluidity of cell membrane has to be precisely regulated, certain membrane transport processes and enzyme activities for ex) cease when the bilayer viscosity is experimentally increased beyond a threshold level - the fluidity of a lipid bilayer depends on BOTH its composition and its tempera- ture -. A synthetic bilayer made from a single type of phospholipid changes from a liquid state to a two-dimensional rigid crystalline (or gel) state at a characteristic temperature. This change of state is called a phase transition, and the temperature at which it occurs is lower (that is, the membrane becomes more difficult to freeze) if the hydrocarbon chains are short or have double bonds. A shorter chain length reduces the tendency of the hydrocarbon tails to interact with one another, in both the same and opposite monolayer, and cis-double bonds produce kinks in the chains that make them more difficult to pack together, so that the membrane remains fluid at lower temperatures (Figure 10-11). -Bacteria, yeasts, and other organisms whose temperature fluctuates with that of their environment adjust the fatty acid com- position of their membrane lipids to maintain a relatively constant fluidity. As the temperature falls, for instance, the cells of those organisms synthesize fatty acids with more cis-double bonds, thereby avoiding the decrease in bilayer fluidity that would otherwise result from the temperature drop. - Cholesterol modulates the properties of lipid bilayers. When mixed with phos- pholipids, it enhances the permeability-barrier properties of the lipid bilayer. Cholesterol inserts into the bilayer with its hydroxyl group close to the polar head groups of the phospholipids, so that its rigid, platelike steroid rings interact with— and partly immobilize—those regions of the hydrocarbon chains closest to the polar head groups - By decreasing the mobility of the first few CH2 groups of the chains of the phospholipid molecules, cholesterol makes the lipid bilayer less deformable in this region and thereby decreases the permeability of the bilayer to small water-soluble molecules. Although choles- terol tightens the packing of the lipids in a bilayer, it does not make membranes any less fluid. At the high concentrations found in most eukaryotic plasma mem- branes, cholesterol also prevents the hydrocarbon chains from coming together and crystallizing. -Thus, lipid bilayers can be built from molecules with similar features but different molecular designs. The plasma membranes of most eukaryotic cells are more varied than those of prokaryotes and archaea, not only in containing large amounts of cholesterol but also in containing a mixture of dif- ferent phospholipids. -While some of this complexity reflects the combinatorial variation in head groups, hydrocarbon chain lengths, and desat- uration of the major phospholipid classes, some membranes also contain many structurally distinct minor lipids, at least some of which have important functions. The inositol phospholipids, for example, are present in small quantities in animal cell membranes and have crucial functions in guiding membrane traffic and in cell signaling (discussed in Chapters 13 and 15, respectively). Their local synthesis and destruction are regulated by a large number of enzymes, which create both small intracellular signaling molecules and lipid docking sites on membranes that recruit specific proteins from the cytosol, as we discuss later.

Proteins Can Move Between Compartments in Different Ways:

- the synthesis of all proteins begins on ribosomes in the cytosol, except for a few that are synthesized on the ribosomes of mitochondria and plastids > their subsequent fate depends on their amino acid sequence, which can contain SORTING SIGNALS that direct their delivery to locations outside the cytosol or to organelle surfaces. - some proteins do NOT have a sorting signal and thus remain the systole PERMANENTLY - many others, however, have specific sorting signals that direct their transport from the cytosol into the nucleus, the ER, mitochondria, plastids, or peroxisomes; SORTING SIGNALS can also direct the transport of proteins from the ER to other destinations in the cell.

Chp 10: Lipid Droplets Are Surrounded By a Phospholipid Monolayer

I. Most cells store an excess of lipids in lipid droplets, from where they can be retrieved as building blocks or as a food source. Fat cells, or adipocytes, are specialized for lipid storage. II. They contain a giant lipid droplet that fills up most of their cytoplasm. Most other cells have many smaller lipid droplets, the number and size varying with the cell's metabolic state. Fatty acids can be liberated from lipid droplets on demand and exported to other cells through the bloodstream. III. Lipid droplets store neutral lipids, such as triacylglycer- ols and cholesterol esters, which are synthesized from fatty acids and cholesterol by enzymes in the endoplasmic reticulum membrane. Because these lipids do not contain hydrophilic head groups, they are exclusively hydrophobic molecules, and therefore aggregate into three-dimensional droplets rather than into bilayers IV.Lipid droplets are unique organelles in that they are surrounded by a single monolayer of phospholipids, which contains a large variety of proteins. Some of the proteins are enzymes involved in lipid metabolism, but the functions of most are unknown. Lipid droplets form rapidly when cells are exposed to high con- centrations of fatty acids. They are thought to form from discrete regions of the endoplasmic reticulum membrane where many enzymes of lipid metabolism are concentrated. Figure 10-14 shows one model of how lipid droplets may form and acquire their surrounding monolayer of phospholipids and proteins. --------- > Figure 10-14 a model for the formation of lipid droplets. neutral lipids are deposited between the two monolayers of the endoplasmic reticulum membrane. there, they aggregate into a three-dimensional droplet, which buds and pinches off from the endoplasmic reticulum membrane as a unique organelle, surrounded by a single monolayer of phospholipids and associated proteins. >

Most Organelles Cannot Be Constructed De Novo: They Require Information in the Organelle Itself

- when a cell reproduces by dividsion, it has to duplicate its organelles, in addition to its chromosomes. Generally, cells do these by incorporating new molecules into existing organelles, thereby enlarging them; the enlarged organelles then divide and are distributed to the two daughter cells -> thus, each daughter cell inherits a complete set of specialized cell membranes from its mother. This inheritance is essential because a cell could NOT make such membranes from scratch. -- > If the Er were completely removed from a cell, ex) how could the cell reconstruct it? A: As we discuss, the membrane proteins that define the ER & perform many of its functions are themselves products of the ER; a new ER could NOT be made without an existing ER or, at least, a membrane that specifically contains the protein translators required to import selected proteins into the ER from the cytosol (including the ER -specific translocators themselves) < same is true for mitochondria and plastids) --- So, it seems info required to construct an organelle does not reside exclusively in the DNA that specifies the organelle's proteins; info in the form of at least on e distinct protein that preexists in the organelle membrane is also required, & this info is passed from part cell to daughter cells in the form of the organelle itself. Presumably, such info is essential for the propagation of the cell's compartmental organization, just as the info in DNA is essential for the propagation of the cell's nucleotide and amino acid sequences. ---- As we discuss later, however, the ER buds off a constant stream of transport vesicles that incorporate only a subset of ER proteins and therefore have a composition different from ER itself. > Similarly, the plasma membrane constantly buds off various types of specialized endocytic vesicles. Thus, some organelles can form from other organelles and do not have to be inherited at cell division.

the evolutionary schemes just described above group the intracellular compartments in eukaryotic cells into four distinct families:

1) the nucleus and cytosol, which communicate w/ each other through nuclear pore complexes and are thus topologically continuous ( although functionally distinct) 2) all organelles that function in the secretory and endocytic pathways- including the ER, Golgi apparatus, endosomes, and lysosomes, the numerous classes of transport intermediates such as transport vesicles that move in between them, and peroxisomes, 3) the mitochondria 4) the plastids (in plants only) ------ Figure 12-3 One suggested pathway for the evolution of the eukaryoticcell and its internal membranes as discussed in Chapter 1, there is evidence that the nuclear genome of a eukaryotic cell evolved from an ancient archeaon.for example, clear homologs of actin, tubulin, histones, and the nuclear Dna replication system are found in archaea, but not in bacteria. Thus, it is now thought that the first eukaryotic cells arose whenan ancient anaerobic archaeon joined forces with an aerobic bacterium roughly 1.6 billion years ago. as indicated, the nuclear envelope may have originated from an invagination of the plasma membraneof this ancient archaeon—an invagination that protected its chromosome while still allowing access of the Dna to the cytosol (as required for Dna to direct protein synthesis). This envelope may have later pinched off completely from the plasma membrane, so as to produce a separate nuclear compartment surrounded by a double membrane. Because this double membrane is penetrated by nuclear pore complexes, the nuclear compartment is topologically equivalent to the cytosol. in contrast, the lumen of the er is continuous with the space between the inner and outer nuclear membranes, and it is topologically equivalent to the extracellular space

Three Mechanisms of Sorting Signals: 3 fundamentally different ways by which proteins move from one compartment to another: GATED TRANSPORT

1. GATED TRANSPORT: proteins and RNA molecules move btw. the cytosol & nucleus through nuclear pore complexes in the nuclear envelope; the nuclear pore complexes function as selective gates that support the active transport of specific macromolecules and macromolecular assemblies between the two topologically equivalent spaces; although they also allow free diffusion of smaller molecules

Nuclear Pore Complexes Perforate the Nuclear Envelope:

1. Large and elaborate NUCLEAR PORE COMPLEXES (NPCs) perforate the nuclear envelope in all eukaryotes; each NPC is composed of a set of ~ 30 different proteins or NUCLEOPORINS > reflecting the high degree of internal symmetry, each nucleoporins is present t in ,multiple copies, resulting in 500-1000 protein molecules in the fully assembled NPC, w/ an estimated mass of 66 million daltons in yeast & 125 million daltons in vertebrates. < most núcleo-orins are composed of repetitive protein domains of only a few different types, which have evolved through extensive gene duplication. Some of the scaffold nuceloporins are structurally related to the vesicle coat protein complexes, such as clathrin and COPII coatomer which shape transport vesicles, and one protein is used as a common building block in both NPCS and vesicle coats, these similarities suggest a common evolutionary origin for the NPCs and vesicle coats: they may derive from an early membrane-bending protein module that helped shape the elaborate membrane system of eukaryotic cells, and in present-day cells stabilize the shaprp membrane bends required to form a nuclear pore/ ---- >The nuclear envelope of a typical mammalian cell contains 3000-4000 NPCs, although that number varies widely, from a few hundred in glial cells to almost 20,000 in Purkinje neurons. The total traffic that passes through each NPC is enor- mous: each NPC can transport up to 1000 macromolecules per second and can transport in both directions at the same time. How it coordinates the bidirectional flow of macromolecules to avoid congestion and head-on collisions is not known. --- >

Chapter 10:phospholipids Spontaneously Form Bilayers

1. The shape and amphiphilic nature of the phospholipid molecules cause them to form bilayers spontaneously in aqueous environments. As discussed in Chapter 2, hydrophilic molecules dissolve readily in water because they contain charged groups or uncharged polar groups that can form either favorable electrostatic interactions or hydrogen bonds with water molecules 2. Hydro- phobic molecules, by contrast, are insoluble in water because all, or almost all, of their atoms are uncharged and nonpolar and therefore cannot form energeti- cally favorable interactions with water molecules. If dispersed in water, they force the adjacent water molecules to reorganize into icelike cages that surround the hydrophobic molecule (Figure 10-6B). Because these cage structures are more ordered than the surrounding water, their formation increases the free energy. This free-energy cost is minimized, however, if the hydrophobic molecules (or the hydrophobic portions of amphiphilic molecules) cluster together so that the smallest number of water molecules is affected 3. When amphiphilic molecules are exposed to an aqueous environment,They spontaneously aggregate to bury their hydrophobic tails in the interior, where they are shielded from the water, and they expose their hydrophilic heads to water. Depending on their shape, they can do this in either of two ways: they can form spherical micelles, with the tails inward, or they can form double-layered sheets, or bilay- ers, with the hydrophobic tails sandwiched between the hydrophilic head group 4. The same forces that drive phospholipids to form bilayers also provide a self-sealing property. A small tear in the bilayer creates a free edge with water; because this is energetically unfavorable, the lipids tend to rearrange sponta- neously to eliminate the free edge. (In eukaryotic plasma membranes, the fusion of intracellular vesicles repairs larger tears.) The prohibition of free edges has a profound consequence: the only way for a bilayer to avoid having edges is by closing in on itself and forming a sealed compartment -This behavior, fundamental to the creation of a living cell, follows directly from the shape and amphiphilic nature of the phospholipid molecule. A lipid bilayer also has other characteristics that make it an ideal structure for cell membranes. One of the most important of these is its fluidity, which is crucial to many membrane functions

Chp 10: The Asymmetry of the Lipid Bilayer is Functionally Important

I. The lipid compositions of the two monolayers of the lipid bilayer in many mem- branes are strikingly different. In the human red blood cell (erythrocyte) mem- brane, for example, almost all of the phospholipid molecules that have cho- line—(CH3)3N+CH2CH2OH—in their head group (phosphatidylcholine and sphingomyelin) are in the outer monolayer, whereas almost all that contain a terminal primary amino group (phosphatidylethanolamine and phosphatidylser- ine) are in the inner monolayer (Figure 10-15). Because the negatively charged phosphatidylserine is located in the inner monolayer, there is a significant dif- ference in charge between the two halves of the bilayer. We discuss in Chapter 12 how membrane-bound phospholipid translocators generate and maintain lipid asymmetry. II. Lipid asymmetry is functionally important, especially in converting extra- cellular signals into intracellular ones (discussed in Chapter 15). Many cytosolic proteins bind to specific lipid head groups found in the cytosolic monolayer of the lipid bilayer. The enzyme protein kinase C (PKC), for example, which is acti- vated in response to various extracellular signals, binds to the cytosolic face of the plasma membrane, where phosphatidylserine is concentrated, and requires this negatively charged phospholipid for its activity. III. In other cases, specific lipid head groups must first be modified to create pro- tein-binding sites at a particular time and place. One example is phosphatidyli- nositol (PI), one of the minor phospholipids that are concentrated in the cytosolic monolayer of cell membranes (see Figure 13-10A-C). Various lipid kinases can add phosphate groups at distinct positions on the inositol ring, creating binding sites that recruit specific proteins from the cytosol to the membrane. An important example of such a lipid kinase is phosphoinositide 3-kinase (PI 3-kinase), which is activated in response to extracellular signals and helps to recruit specific intracellular signaling proteins to the cytosolic face of the plasma membrane. Similar lipid kinases phosphorylate inositol phospholipids in intracellular membranes and thereby help to recruit proteins that guide membrane transport. III. Phospholipids in the plasma membrane are used in yet another way to con- vert extracellular signals into intracellular ones. The plasma membrane contains various phospholipases that are activated by extracellular signals to cleave spe- cific phospholipid molecules, generating fragments of these molecules that act as short-lived intracellular mediators. Phospholipase C, for example, cleaves an inositol phospholipid in the cytosolic monolayer of the plasma membrane to gen- erate two fragments, one of which remains in the membrane and helps activate protein kinase C, while the other is released into the cytosol and stimulates the release of Ca2+ from the endoplasmic reticulum. -Phospholipase C, for example, cleaves an inositol phospholipid in the cytosolic monolayer of the plasma membrane to generate two fragments, one of which remains in the membrane and helps activate protein kinase C, while the other is released into the cytosol and stimulates the release of Ca2+ from the endoplasmic reticulum IV. Animals exploit the phospholipid asymmetry of their plasma membranes to distinguish between live and dead cells. When animal cells undergo apoptosis (a form of programmed cell death, discussed in Chapter 18), phosphatidylserine, which is normally confined to the cytosolic (or inner) monolayer of the plasma membrane lipid bilayer, rapidly translocates to the extracellular (or outer) mono- layer. The phosphatidylserine exposed on the cell surface signals neighboring cells, such as macrophages, to phagocytose the dead cell and digest it. The trans- location of the phosphatidylserine in apoptotic cells is thought to occur by two mechanisms: 1. The phospholipid translocator that normally transports this lipid from the outer monolayer to the inner monolayer is inactivated. 2. A "scramblase" that transfers phospholipids nonspecifically in both direc- tions between the two monolayers is activated.

More on Organelles:

1. abundance & shape of membrane-enclosed organelles are regulated to meet the needs of the cell; 2. This is particularly apparent in cells that are highly specialized + therefore disproportionately rely on specific organelles. - eg) plasma cells, which secrete their own weight every day in antibody molecules into the bloodstream, contain vastly amplified amounts of rough ER, which is found in large, flat sheets. - cells that specialize in lipid synthesis also expand their ER, but in this case, the organelle forms a network of convoluted tubules. -Moreover, membrane-enclosed organelles are often found in characteristics positions in the cytoplasm. - in most cells, ex) the Golgi apparatus is located close to the nucleus, whereas the network of ER tubules extends from the nucleus t/o the entire cytosol. > these characteristic distributions depend on interactions of the organelles w/ the cytoskeleton: - the localization of both the ER and the Golgi apparatus depends on an intact microtubule array; if the microtubules are experimentally depolymerized w/ a drug, the Golgi apparatus fragments & disperses t/o the cell & the ER network collapses toward the cell center >> the size, shape, composition, & location are all important & regulated features of these organelles that ultimately contribute to the organelle's function

Three Mechanisms of Sorting Signals: 3 fundamentally different ways by which proteins move from one compartment to another: PROTEIN TRANSLOCATION

2. In protein translocation, transmembrane protein translators directly transport specific proteins across a membrane from the cytosol into a space that's topologically distinct ; - the transported protein molecule usually must unfold to snake through the translator; the initial transport of selected proteins from the cytosol into the ER lumen or mitochondria occurs in this way - integral membrane proteins often use the same translators but translocate only partially across the membrane, so that the protein becomes embedded in the lipid bilayer

The Transport of Molecules Between the Nucleus and the Cytosol:

> the NUCLEAR ENVELOPE encloses the DNA & defines the nuclear compartment; this envelope consists of two concentric membranes, which are penetrated by nuclear pore complexes. > Although the inner & outer nuclear membranes are continuous, they maintain distinct protein compositions. >The INNER NUCLEAR MEMBRANE contains proteins that act as binding sites for chromosomes and for the nuclear lamina, a protein meshwork that provides structural support for the nuclear envelope; the lamina also acts as an anchoring site for chromosomes and the cytoplasmic cytoskeleton (via protein complexes that span the nuclear envelope). > the OUTER NUCLEAR MEMBRANE which is continuous with the membrane of the ER; like the ER membrane, the outer nuclear membrane is studded with ribosomes engaged in protein synthesis. **The proteins made on these ribosomes are transported into the space btw. the inner and outer nuclear membrane ( the perinuclear space), which is continuous w/ the ER lumen - BIDIRECTIONAL traffic occurs continuously between the cytosol and nucleus; the many proteins that function in the nucleus-including histones, DNA polymerases, RNA polymerases, transcriptional regulators, and RNA-processing proteins - are selectively imported into the nuclear compartment from the cytosol, where they are made. @ the same time, almostt all RNAS- including mRNAS, rRNAS, tRNAS, miRNAS, and snRNAs - are synthesized in the nuclear compartment & then exported to the cytosol; like the import process, the export process is selective; mRNAS are exported ONLY AFTER they've been properly modified by RNA-processing reactions in the nucleus - in some cases, the transport process is complex, ribosomal proteins made in the cytosol and imported into the nucleus, where they assemble w/ newly made ribosomal RNA into particles. - the particles are then exported to the cytosol, where they assemble into ribosomes. Each of these steps requires selective transport across the nuclear envelope

Chapter 10: The Lipid Bilayer is a 2D Fluid

Around 1970, researchers first recognized that individual lipid molecules are able to diffuse freely within the plane of a lipid bilayer. The initial demonstration came from studies of synthetic (artificial) lipid bilayers, which can be made in the form of spherical vesicles, called liposomes (Figure 10-9); or in the form of planar bilayers formed across a hole in a partition between two aqueous compartments or on a solid support. 1. Various tech have been used to measure the motion of individual lipid molecules and their components; one can construct s lipid molecule, for ex) with a fluorescent dye or a small gold particle attached to its polar head group and follow the diffusion of even individual molecules in a membrane. Alternatively, one can modify a lipid head group to carry a "spin label" such as nitride group (=N-O); this contains an unpaired electron whose spin creates a paramag- netic signal that can be detected by electron spin resonance (ESR) spectroscopy, the principles of which are similar to those of nuclear magnetic resonance (NMR), discussed in Chapter 8. The motion and orientation of a spin-labeled lipid in a bilayer can be deduced from the ESR spectrum. 2. Such studies show that phospho- lipid molecules in synthetic bilayers very rarely migrate from the monolayer (also called a leaflet) on one side to that on the other. This process, known as "flip-flop," occurs on a time scale of hours for any individual molecule, although cholesterol is an exception to this rule and can flip-flop rapidly. In contrast, lipid molecules rapidly exchange places with their neighbors within a monolayer (~107 times per second). This gives rise to a rapid lateral diffusion, with a diffusion coefficient (D) of about 10-8 cm2/sec, which means that an average lipid molecule diffuses the length of a large bacterial cell (~2 μm) in about 1 second 3. These studies have also shown that individual lipid molecules rotate very rapidly about their long axis and have flexible hydrocarbon chains. Computer simulations show that lipid mole- cules in synthetic bilayers are very disordered, presenting an irregular surface of variously spaced and oriented head groups to the water phase on either side of the bilayer (Figure 10-10). 4. Similar mobility studies on labeled lipid molecules in isolated biological membranes and in living cells give results similar to those in synthetic bilayers. They demonstrate that the lipid component of a biological membrane is a two-di- mensional liquid in which the constituent molecules are free to move laterally. As in synthetic bilayers, individual phospholipid molecules are normally confined to their own monolayer. This confinement creates a problem for their synthesis. Phospholipid molecules are manufactured in only one monolayer of a membrane, mainly in the cytosolic monolayer of the endoplasmic reticulum membrane. If none of these newly made molecules could migrate reasonably promptly to the noncytosolic monolayer, new lipid bilayer could not be made. The problem is solved by a special class of membrane proteins called phospholipid translocators, or flippases, which catalyze the rapid flip-flop of phospholipids from one mono- layer to the other, ---- 5. Despite the fluidity of the lipid bilayer, liposomes do not fuse spontaneously with one another when suspended in water. Fusion does not occur because the polar lipid head groups bind water molecules that need to be displaced for the bilayers of two different liposomes to fuse. The hydration shell that keeps lipo- somes apart also insulates the many internal membranes in a eukaryotic cell and prevents their uncontrolled fusion, thereby maintaining the compartmen- tal integrity of membrane-enclosed organelles. -All cell membrane fusion events are catalyzed by tightly regulated fusion proteins, which force appropriate mem- branes into tight proximity, squeezing out the water layer that keeps the bilayers apart,

Summary

Biological membranes consist of a continuous double layer of lipid molecules in which membrane proteins are embedded. This lipid bilayer is fluid, with individual lipid molecules able to diffuse rapidly within their own monolayer. The membrane lipid molecules are amphiphilic. When placed in water, they assemble sponta- neously into bilayers, which form sealed compartments. Although cell membranes can contain hundreds of different lipid species, the plasma membrane in animal cells contains three major classes—phospholipids, cholesterol, and glycolipids. Because of their different backbone structure, phos- pholipids fall into two subclasses—phosphoglycerides and sphingolipids. The lipid compositions of the inner and outer monolayers are different, reflecting the different functions of the two faces of a cell membrane. Different mixtures of lipids are found in the membranes of cells of different types, as well as in the various membranes of a single eukaryotic cell. Inositol phospholipids are a minor class of phospholipids, which in the cytosolic leaflet of the plasma membrane lipid bilayer play an import- ant part in cell signaling: in response to extracellular signals, specific lipid kinases phosphorylate the head groups of these lipids to form docking sites for cytosolic sig- naling proteins, whereas specific phospholipases cleave certain inositol phospho- lipids to generate small intracellular signaling molecules.

Organelles: Peroxisomes

small vesicular compartments that contain enzymes used in various oxidative reactions --- * in general, each membrane-enclosed organelle performs the same set of basic function sin all cell types; but to serve the specialized functions of cells, these organelles VARY in ABUNDANCE and can have additional properties that differ from cell type to cell type. *On average, the membrane-enclosed compartments together occupy nearly half the volume of a cell (Table 12-1), and a large amount of intracellular mem- brane is required to make them. In liver and pancreatic cells, for example, the endoplasmic reticulum has a total membrane surface area that is, respectively, 25 times and 12 times that of the plasma membrane (Table 12-2). The mem- brane-enclosed organelles are packed tightly in the cytoplasm, and, in terms of area and mass, the plasma membrane is only a minor membrane in most eukary- otic cells (Figure 12-2).

sizing of nuclear pores:

Each NPC contains aqueous passages, through which small water-soluble molecules can diffuse passively. Researchers have determined the effective size of these passages by injecting labeled water-soluble molecules of different sizes into the cytosol and then measuring their rate of diffusion into the nucleus. Small molecules (5000 daltons or less) diffuse in so fast that we can consider the nuclear envelope freely permeable to them. Large proteins, however, diffuse in much more slowly, and the larger a protein, the more slowly it passes through the NPC. Proteins larger than 60,000 daltons cannot enter by passive diffusion. This size cut-off to free diffusion is thought to result from the NPC structure (see Figure 12-8). The channel nucleoporins with extensive unstructured regions form a dis- ordered tangle (much like a kelp bed in the ocean) that restrictsthe diffusion of large macromolecules while allowing smaller molecules to pass. ---- Because many cell proteins are too large to diffuse passively through the NPCs, the nuclear compartment and the cytosol can maintain different protein compo- sitions. Mature cytosolic ribosomes, for example, are about 30 nm in diameter and thus cannot diffuse through the NPC, confining protein synthesis to the cyto- sol. But how does the nucleus export newly made ribosomal subunits or import large molecules, such as DNA polymerases and RNA polymerases, which have subunit molecular masses of 100,000-200,000 daltons? As we discuss next, these and most other transported protein and RNA molecules bind to specific receptor proteins that actively ferry large molecules through NPCs. Even small proteins like histones frequently use receptor-mediated mechanisms to cross the NPC, thereby increasing transport efficiency

SORTING SIGNALS & SORTING RECEPTORS

Each mode of protein transfer is usually guided by sorting signals in the trans- ported protein, which are recognized by complementary sorting receptors. >> If a large protein is to be imported into the nucleus, for example, it must possess a sorting signal that receptor proteins recognize to guide it through the nuclear pore complex. >>If a protein is to be transferred directly across a membrane, it must pos- sess a sorting signal that the translocator recognizes. >>Likewise, if a protein is to be loaded into a certain type of vesicle or retained in certain organelles, a complementary receptor in the appropriate membrane must recognize its sorting signal.

Summary:

Eukaryotic cells contain intracellular membrane-enclosed organelles that make up nearly half the cell's total volume. The main ones present in all eukaryotic cells are the endoplasmic reticulum, Golgi apparatus, nucleus, mitochondria, lysosomes, endosomes, and peroxisomes; plant cells also contain plastids such as chloroplasts. These organelles contain distinct sets of proteins, which mediate each organelle's unique function. Each newly synthesized organelle protein must find its way from a ribosome in the cytosol, where the protein is made, to the organelle where it functions. It does so by following a specific pathway, guided by sorting signals in its amino acid sequence that function as either signal sequences or signal patches. Sorting signals are recognized by complementary sorting receptors, which deliver the protein to the appropriate target organelle. Proteins that function in the cytosol do not contain sorting signals and therefore remain there after they are synthesized. During cell division, organelles such as the ER and mitochondria are distributed to each daughter cell. These organelles contain information that is required for their construction, and so they cannot be made de novo.

Chapter 2: Lipid Aggregates, Phospholipids

I. Fatty acids have a hydrophilic head and a hydrophobic tail, in H2O they can form a surface film or form small micelles - their derivatives can form larger aggregates held together by HYDROPHOBIC forces: 1. triacylglycerols (triglycerides) can form large spherical fat droplets in the cell cytoplasm 2. phospholipids and glycolipids form self-sealing lipid bilayers that are the basis for all cell membranes. ---- other lipids: lipids are defined as the water-insoluble molecules in cells that are soluble in organic solvents; two other common types of lipid are steroids and polyisoprenoids ( long chain polymers of isoprene). Both are made from isoprene units: - steroids: have a common multiple-ring structure: cholesterol found in many membranes, testosterone- male steroid hormone ------ Glycolipids: Like phospholipids, these compounds are composed of a hydrophobic region containing two long hydrocarbon tails and a polar region, which contains one or more sugars, and unlike phospholipids, no phosphate. --- dolichol phosphate- used to carry activated sugars in the membrane-associated synthesis of glycoproteins and some polysaccharides.

Chapter 3: Proteins Often Form Large Complexes that Function as Protein Machines:

I. Large proteins formed from many domains are able to perform more elaborate functions s than small, single-domain proteins. -But large protein assemblies formed from many protein molecules linked together by non covalent bonds perform the most impressive tasks. - now that it's possible to reconstruct most biological processes in cell-free systems in the lab, it's clear that each of the central processes in a cell- such as DNA replication, protein synthesis, vesicle budding, or transmembrane signaling- is catalyzed by a highly coordinated, linked set of 10 or more proteins. -> In most such PROTEIN MACHINES, an energetically favorable reaction such as the hydrolysis of bound nucleoside triphosphate (ATP or GTP_ drives an ordered series of conformational changes in one or more of the individual protein subunits, enabling the ensemble of proteins to move coordinately. In this way, each enzyme can be moved directly into position, as the machine catalyzes successive reactions in a series. This is what occurs for ex) in protein synthesis on a ribosome or in DNA ex) replication where a largee multi protein complex moves rapidly along the DNA -

Section Notes: All Eukaryotic Cells Have the Same Basic Set of Membrane-enclosed Organelles:

I. Many processes take place in membranes or on their surfaces; membrane-bound enzymes ex) catalyze lipid metabolism & oxidative phosphorylation & photosynthesis theses both require a membrane to couple the transport of H+ to the synthesis of ATP. II. Along w/ providing increased membrane area to host biochem reactions, intracellular membrane systems form enclosed compartments that are separate from the cytosol, thus creating functionally-specialized aqueous spaces within the cell. Ion those spaces, subsets of molecules (proteins, reactant, ions) are concentrated to optimize the biochemical reactions in which they participate. III. Because the lipid bilayer of cell membranes's impermeable to most hydrophilic molecules, the membrane of an organelle must contain membrane-transport proteins to import and export specific metabolites. Each organelle membrane must also have a mechanism foer importing, and incorporating into the organelle, the specific proteins that makes the organelle unique.

Evolutionary Origins May Help the Topological Relationships of Organelles:

I. The precursors of the first eukaryotic cells are thought to have been relatively simple cells that - like most bacterial & archaeal cells- have a plasma membrane but NO internal membranes: - the PLASMA MEMBRANE in such cells provides all MEMBRANE-DEPENDENT functions including the pumping of ions, ATP synthesis, protein secretion, & lipid synthesis II. typical present-day eukaryotic cells are 10-30 times larger in linear dimension and 1,00-10,000 times greater in volume than a typical bacterium such as E. coli' the profusion of internal membranes can be regarded, in part, as an adaptation to this increase in size: the eukaryotic cell has a much smaller ratio of surface area area to volume, & its plasma membrane therefore presumably has too small an area to sustain the many vital functions that membranes perform; the extensive internal membrane systems of a eukaryotic cell alleviate this problem III. a hypothetical scheme for how the first eukaryotic cells, with a nucleus and ER, might have evolved by the invagination and pinching off the plasma membrane of an ancestral cell; this process would create membrane-enclosed organelles with an interior or LUMEN that's topologically equivalent to the exterior of the cell ^ this topological relationship holds for alll of the organelles involved in the secretory and endocytic pathways, including the Erm Golgi apparatus, endosomes, lysosomes, & peroxisomes. > their interiors communicate extensively w/ one another and with the outside of the cell via TRANSPORT VESICLES, which bud off from one organelle and fuse with another

Ch 3: Scaffolds Concentrate Sets of Interacting Proteins

I. protein machines are often very localized to specific sites in the cell, being assembled and activated only where and when they are needed. II. ex) when extracellular signaling molecules bind to receptor proteins in the plasma membrane, the activated receptors often recruit a set of other proteins to the inside surface of the plasma membrane to form a large protein complex that passes the signal on. III. The mechanisms frequently involve SCAFFOLD PROTEINS, these are proteins w/ binding sites for multiple other proteins, and they serve both to link together specific sets of interacting proteins and to position them at specific locations inside a cell. - at one extreme are rigid scarrgolds, such as the cullin in SCF ubiquitin ligase - at the other extreme are large, flexible scaffold proteins that often underlie regions of specialized plasma membrane. These include the DISCS-LARGE Protein (DLG) protein of about 900 amino acids that's concentrated in special regions beneath the plasma membrane in epithelial cells and at synapses. Dlg contains binding sites for at least 6 other proteins, interspersed w. regions of more flexible polypeptide chain. An ancient protein, conserved in organisms as diverse as sponges, worms, flies, and humans, Dog derives its name from the mutant phenotype of the organism in which it was first discovered; the cells in the imaginal discs of a Drosophila embryo with a mutation in the Dlg gene fail to stop proliferating when they should, and they produce unusually large discs whose epithelial cells can form tumors. Although incompletely studied, Dlg and a large number of similar scaffold proteins are thought to function like the protein that is schematically illustrated in Figure 3-78. > By binding a specific set of interacting proteins, these scaffolds can enhance the rate of critical reactions, while also confining them to the particular region of the cell that contains the scaffold. For similar reasons, cells also make extensive use of scaffold RNA molecules, as discussed in Chapter 7. >Figure 3-78 How the proximity created by scaffold proteins can greatly speed reactions in a cell. In this example, long unstructured regions of polypeptide chain in a large scaffold protein connect a series of structured domains that bind a set of reacting proteins. The unstructured regions serve as flexible "tethers" that greatly speed reaction rates by causing a rapid, random collision of all of the proteins that are bound to the scaffold --- Figure 3-77 How "protein machines" carry out complex functions. These machines are made of individual proteins that collaborate to performa specific task (Movie 3.13). The movement of these proteins is often coordinated by the hydrolysis of a bound nucleotide such as ATP or GTP. Directional allosteric conformational changes of proteins that are driven in this way often occur in a large protein assembly in which the activities of several different protein molecules are coordinated by such movements within the complex

Chp 10: Glycolipids are found on the surface of all Eukaryotic Plasma Membranes

I.Sugar-containing lipid molecules called glycolipids have the most extreme asym- metry in their membrane distribution: these molecules, whether in the plasma membrane or in intracellular membranes, are found exclusively in the monolayer facing away from the cytosol. II.In animal cells, they are made from sphingosine, just like sphingomyelin (see Figure 10-3). These intriguing molecules tend to self-as- sociate, partly through hydrogen bonds between their sugars and partly through van der Waals forces between their long and straight hydrocarbon chains, which causes them to partition preferentially into lipid raft phases III. The asymmetric distribution of glycolipids in the bilayer results from the addi- tion of sugar groups to the lipid molecules in the lumen of the Golgi apparatus. Thus, the compartment in which they are manufactured is topologically equiv- alent to the exterior of the cell (discussed in Chapter 12). As they are delivered to the plasma membrane, the sugar groups are exposed at the cell surface (see Figure 10-15), where they have important roles in interactions of the cell with its surroundings. IV. Glycolipids probably occur in all eukaryotic cell plasma membranes, where they generally constitute about 5% of the lipid molecules in the outer monolayer. They are also found in some intracellular membranes. The most complex of the glycolipids, the gangliosides, contain oligosaccharides with one or more sialic acid moieties, which give gangliosides a net negative charge V. Hints as to the functions of glycolipids come from their localization. In the plasma membrane of epithelial cells, for example, glycolipids are confined to the exposed apical surface, where they may help to protect the membrane against the harsh conditions frequently found there (such as low pH and high concen- trations of degradative enzymes). Charged glycolipids, such as gangliosides, may be important because of their electrical effects: their presence alters the electrical field across the membrane and the concentrations of ions—especially Ca2+—at the membrane surface. Glycolipids also function in cell-recognition processes, in which membrane-bound carbohydrate-binding proteins (lectins) bind to the sugar groups on both glycolipids and glycoproteins in the process of cell-cell adhesion (discussed in Chapter 19). Mutant mice that are deficient in all of their complex gangliosides show abnormalities in the nervous system, including axonal degeneration and reduced myelination. ----Some glycolipids provide entry points for certain bacterial toxins and viruses. The ganglioside GM1 (see Figure 10-16), for example, acts as a cell-surface recep- tor for the bacterial toxin that causes the debilitating diarrhea of cholera. Cholera toxin binds to and enters only those cells that have GM1 on their surface, including intestinal epithelial cells. Its entry into a cell leads to a prolonged increase in the concentration of intracellular cyclic AMP (discussed in Chapter 15), which in turn causes a large efflux of Cl-, leading to the secretion of Na+, K+, HCO3-, and water into the intestine. Polyomaviruses also enter the cell after binding initially to gan- gliosides.

Nuclear Localization Signal (NLS) Direct Nuclear Proteins to the Nucleus:

I.When proteins are experimentally extracted from the nucleus and reintroduced into the cytosol, even the very large ones reaccumulate efficiently in the nucleus. Sorting signals called nuclear localization signals (NLSs) are responsible for the selectivity of this active nuclear import process. II. The signals have been precisely defined by using recombinant DNA technology for numerous nuclear proteins, as well as for proteins that enter the nucleus only transiently (Figure 12-9). In many nuclear proteins, the signals consist of one or two short sequences that are rich in the positively charged amino acids lysine and arginine (see Table 12-3, p. 648), with the precise sequence varying for different proteins. Other nuclear proteins contain different signals, some of which are not yet characterized. III. Nuclear localization signals can be located almost anywhere in the amino acid sequence and are thought to form loops or patches on the protein surface. Many function even when linked as short peptides to lysine side chains on the surface of a cytosolic protein, suggesting that the precise location of the signal within the amino acid sequence of a nuclear protein is not important. Moreover, as long as one of the protein subunits of a multicomponent complex displays a nuclear localization signal, the entire complex will be imported into the nucleus. >One can visualize the transport of nuclear proteins through NPCs by coating gold particles with a nuclear localization signal, injecting the particles into the cytosol, and then following their fate by electron microscopy (Figure 12-10). The particles bind to the tentaclelike fibrils that extend from the scaffold nucleoporins at the rim of the NPC into the cytosol, and then proceed through the center of the NPC. Presumably, the unstructured regions of the nucleoporins that form a diffu- sion barrier for large molecules (mentioned earlier) are pushed away to allow the coated gold particles to squeeze through. Macromolecular transport across NPCs differs fundamentally from the transport of proteins across the membranes of other organelles, in that it occurs outer nuclear membrane >through a large, expandable, aqueous pore, rather than through a protein trans- porter spanning one or more lipid bilayers. For this reason, fully folded nuclear proteins can be transported into the nucleus through an NPC, and newly formed ribosomal subunits are transported out of the nucleus as an assembled particle. By contrast, proteins have to be extensively unfolded to be transported into most other organelles, as we discuss later.

Three Mechanisms of Sorting Signals: 3 fundamentally different ways by which proteins move from one compartment to another: VESICULAR TRANSPORT

In VESICULAR TRANSPORT, membrane-enclosed transport intermediates, which may be small, spherical transport vesicles or larger, irregularly shaped organelle fragments- ferry proteins from one topologically equivalent compartment to another > the transport vesicles and fragments become loaded w. a cargo of molecules delivered from one lumen of one compartment as they bud and pinch off from its membrane; they discharge their cargo into a second compartment by fusing w/ the membrane enclosing that compartment. - the transfer of soluble proteins from the ER to the Golgi apparatus happens this way -Because the transported proteins do not cross a membrane, vesicular transport can move proteins only between compartments that are topologically equiva- lent (see Figure 12-4). > Compartments are said to be topologically equivalent if they can communicate with one another, in the sense that molecules can get from oneto the other without having to cross a membrane. Topologically equivalent spaces are shown in red. (a) molecules can be carried from one compartment to another topologically equivalent compartment by vesicles that bud from one and fuse with the other. (B) in principle, cycles of membrane budding and fusion permitthe lumen of any of the organelles shown to communicate with any other and with the cell exterior by means of transport vesicles. Blue arrows indicate the extensive outbound and inbound vesicular traffic (discussed in Chapter 13). some organelles, most notably mitochondria and (in plant cells) plastids, do not take part in this communication and are isolated from the vesicular traffic between organelles shown here.

Ch 10: The Lipid BiLayer: phosphoglycerides, Sphingolipids, and Sterols Are the Major lipids in cell Membranes

The lipid bilayer provides the basic structure for all cell membranes. It is easily seen by electron microscopy, and its bilayer structure is attributable exclusively to the special properties of the lipid molecules, which assemble spontaneously into bilayers even under simple artificial conditions ------ > lipid molecules : Lipid molecules constitute about 50% of the mass of most animal cell membranes, nearly all of the remainder being protein. There are approximately 5 × 106 lipid molecules in a 1 μm × 1 μm area of lipid bilayer, or about 109 lipid molecules in the plasma membrane of a small animal cell > All of the lipid molecules in cell membranes are amphiphilic—that is, they have a hydrophilic ("water-loving") or polar end and a hydrophobic ("water-fearing") or nonpolar end. - The most abundant membrane lipids are the phospholipids. These have a polar head group containing a phosphate group and two hydrophobic hydrocar- bon tails. In animal, plant, and bacterial cells, the tails are usually fatty acids, and they can differ in length (they normally contain between 14 and 24 carbon atoms): 1. One tail typically has one or more cis-double bonds (that is, it is unsaturated), while the other tail does not (that is, it is saturated). As shown in Figure 10-2, each cis-double bond creates a kink in the tail. Differences in the length and sat- uration of the fatty acid tails influence how phospholipid molecules pack against one another, thereby affecting the fluidity of the membrane 2. The main phospholipids in most animal cell membranes are the phospho- glycerides, which have a three-carbon glycerol backbone (see Figure 10-2). Two long-chain fatty acids are linked through ester bonds to adjacent carbon atoms of the glycerol, and the third carbon atom of the glycerol is attached to a phos- phate group, which in turn is linked to one of several types of head group. By combining several different fatty acids and head groups, cells make many different phosphoglycerides. Phosphatidylethanolamine, phosphatidylserine, and phosphatidylcholine are the most abundant ones in mammalian cell membranes ---\ Another important class of phospholipids are the sphingolipids, which are built from sphingosine rather than glycerol (Figure10-3D-E). Sphingosine is a long acyl chain with an amino group (NH2) and two hydroxyl groups (OH) at one end. In sphingomyelin, the most common sphingolipid, a fatty acid tail is attached to the amino group, and a phosphocholine group is attached to the terminal hydroxyl group. Together, the phospholipids phosphatidylcholine, phosphatidylethanol- amine, phosphatidylserine, and sphingomyelin constitute more than half the mass of lipid in most mammalian cell membranes ---- In addition to phospholipids, the lipid bilayers in many cell membranes con- tain glycolipids and cholesterol. Glycolipids resemble sphingolipids, but, instead of a phosphate-linked head group, they have sugars attached. We discuss glyco- lipids later. Eukaryotic plasma membranes contain especially large amounts of cholesterol—up to one molecule for every phospholipid molecule. Cholesterol is a sterol. It contains a rigid ring structure, to which is attached a single polar hydroxyl group and a short nonpolar hydrocarbon chain (Figure 10-4). The cho- lesterol molecules orient themselves in the bilayer with their hydroxyl group close to the polar head groups of adjacent phospholipid molecules

Organelles: Lysosomes

contain digestive enzymes that degrade defunct (no longer in effect or in use) intracellular organelles, as well as macromolecules and particles taken in from outside the cell by ENDOCYTOSIS ( the taking of matter by a living cell by invagination of its membrane to form a vacuole)

organelles: nucleus

contains the genome (aside from mitochondrial and chloroplast DNA), and it is the principal site of DNA and RNA synthesis.

bacterium vs. eukaryotic cell

generally consists of a single intracellular compart- ment surrounded by a plasma membrane vs. elaborately sub- divided into functionally distinct, membrane-enclosed compartments.

Organelles : Mitochondria +Chloroplasts

generate most of the ATP that cells use to drive reactions requiring an input of free energy; - chloroplasts area specialized version of PLASTIDS, present in plants, algae, and some protozoa, which can also have other functions such as the storage of food or pigment molecules.

organelles + proteins

or compartment contains its own characteristic set of enzymes and other specialized molecules and complex distribution systems transport specific products from one compartment to another - proteins confer upon each compartment or organelle: its characteristic structural and functional properties; they catalyze the reactions that occur there and selectively transport small molecules into and out of the organelle --- for membrane-enclosed organelles oil the cytoplasm, proteins too serve as organelle-specific surface markers that direct new deliveries of proteins and lipids to the appropriate organelle.

A simplified road map of protein traffic within a eukaryotic cell:

summary: proteins can move from one compartment to anotherby gated transport (red), protein translocation (blue), or vesicular transport (green). The sorting signals that direct a given protein's movement through the system, and thereby determine its eventual location in the cell, are contained in each protein's amino acid sequence. The journey begins with the synthesis of a protein on a ribosome in the cytosol and, for many proteins, terminates when the protein reaches its final destination. other proteins shuttle back and forth between the nucleus and cytosol. at each intermediate station (boxes), a decision is made as to whether the protein is to be retained in that compartment or transported further. a sorting signal may direct either retention in or exit from a compartment. ----- >gated: cytosol to nucleus > transmembrane transport: cytosol to plastids, cytosol to mitochondria, cytosol to ER, cytosol to peroxisomes > vesicular transport: ER to peroxisomes, ER to golgi, golgi to late endome, golf to early endosome, golgi to secretory vesicles, late endosome to lysosome, early endosome to late endosome, early endorse to cell exterior, secretory vesicles to cell exterior, goggle to cell exterior

More info

the mitochondria and plastids differ from the other membrane-enclosed organelles because they contain their genomes. - the nature of these genomes and the close resemblance of the proteins in these organelles to those in some present-day bacteria, strongly suggest that mitochondria & plastids evolved from bacteria that were engulfed by other cells w/ which they initially lived in symbiosis:he inner membrane of mitochondria and plastids presumably corresponds to the original plasma membrane of the bacterium, while the lumen of these organelles evolved from the bacterial cytosol. - Like the bacteria from which they were derived, both mitochondria and plastids are enclosed by a double membrane and they remain isolated from the extensive vesicular traffic that connects the interiors of most of the other membrane-enclosed organelles to each other and to the outside of the cell.

cytosol

the space of cytoplasm outside the membrane-enclosed organelles and where the synthesis of almost all proteins begins, - each newly synthesized protein is then delivered specifically to the organelle that requires it; the intracellular transport of proteins is the centra

organelles: cytoplasm

the surrounding cytoplasm consists of the cytosol and the cytoplasmic organelles suspended in it; the cytosol constitutes a little more than 1/2 the total volume of the cell, and it is the main site of protein synthesis and degradation; - it also performs most of the cell's intermediary metabolism- that is, the many reactions that degrade some molecules & synthesize others to provide the building blocks for macromolecules

organelles: endoplasmic reticulum

~ About 1/2 the total area of membrane in a eukaryotic cell encloses the labyrinthine spaces of the endoplasmic reticulum (ER): ```````` I. the rough ER: -has many ribosomes bound to its cytosolic surface; - RIBOSOMES are ORGANELLES that are not membrane -enclosed; they synthesize both soluble and integral membrane proteins, most of which are destined either for secretion to the cell exterior or for other organelles * we'll see that whereas proteins are transported into other membrane-enclosed organelles only after their synthesis is complete, they are transported into the ER as they are synthesized. This explains why the ER membrane is unique in having ribosomes tethered to it; the ER also produces most of the lipid for the rest of the cell and functions as a store for Ca^2+ ions. - ----------------------- II. the SMOOTH ER: - regions of the ER that lack bound ribosomes are called smooth ER - the ER sends many of its proteins and lipids to the Golgi apparatus which often consists of organized stacks of disc-like compartments called Golgi cisternae - the Golgi apparatus receives lipids and proteins from the ER & dispatches them to various destinations, usually covalently modifying them en route