Chapter 2- The Cell

Enzymatic receptors

ligand binding induces catalytic activity in associated peripheral proteins.

Neurofilament proteins

make heterodimers that form the subunits of the major intermediate filaments of neurons.

cisternae

-channel that makes up golgi and ER

Vimentin

-intermediate filament protein -most common class III intermediate filament protein -found in most cells derived from embryonic mesenchyme

target cells

Cells bearing receptors for a specific ligand

summary of lysosomal functions

Synthesis of lysosomal enzymes occurs in the RER, with packaging in the Golgi apparatus. Endocytosis produces vesicles that fuse with endosomes before merging with lysosomes. Phagocytic vacuoles (or phagosomes) fuse with primary lysosomes to become secondary lysosomes (or heterolysosomes), in which ingested material is degraded. Autophagosomes, such as those depicted here with a mitochondrion in the process of digestion, are formed after nonfunctional or surplus organelles become enclosed with membrane and the resulting structure fuses with a lysosome. The products of lysosomal digestion are recycled to the cytoplasm, but indigestible molecules remain in a membrane-enclosed residual body, which may accumulate in long-lived cells as lipofuscin. In some cells, such as osteoclasts, the lysosomal enzymes are secreted into a restricted extracellular compartment.

centrosome

The dominant MTOC in most cells. which is organized around two cylindrical centrioles. the paired centrioles organize nearby tubulin complexes and other proteins as a pericentriolar matrix found close to the nucleus of non dividing cells. Before cell division, more specifically during the period of DNA replication, each centrosome duplicates itself so that now each centrosome has two pairs of centrioles. During mitosis, the centrosome divides into halves, which move to opposite poles of the cell, and become organizing centers for the microtubules of the mitotic spindle..

fluid mosaic model

The fluid mosaic model describes the structure of the plasma membrane as a mosaic of components —including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character (a) Two types of cells were grown in tissue cultures, one with fluorescently labeled transmembrane proteins in the plasmalemma (right) and one without. (b) Cells of each type were fused together experimentally into hybrid cells. (c) Minutes after the fusion of the cell membranes, the fluorescent proteins of the labeled cell spread to the entire surface of the hybrid cells. Such experiments provide important data supporting the fluid mosaic model. However, many membrane proteins show more restricted lateral movements, being anchored in place by links to the cytoskeleton.

Intermediate Filaments

The third class of cytoskeletal components, filaments intermediate in size between the other two. stable, confer increased mechanical stability to cell structure, and are made up of different protein subunits in different cell types. MEDICAL APPLICATION The presence of a specific type of intermediate filament in tumors can often reveal the cellular origin of the tumor, information important for diagnosis and treatment of the cancer. Identification of intermediate filament proteins by means of immunocytochemical methods is a routine procedure. One example is the use of GFAP to identify astrocytomas, the most common type of brain tumor.

RER in different cells

The ultrastructure and general histologic appearance of a cell are determined by the nature of the most prominent proteins the cell is making. (a) Cells that make few or no proteins for secretion have very little RER, with essentially all polyribosomes free in the cytoplasm. (b) Cells that synthesize, segregate, and store various proteins in specific secretory granules or vesicles always have RER, a Golgi apparatus, and a supply of granules containing the proteins ready to be secreted. (c) Cells with extensive RER and a well-developed Golgi apparatus show few secretory granules because the proteins undergo exocytosis immediately after Golgi processing is complete. Many cells, especially those of epithelia, are polarized, meaning that the distribution of RER and secretory vesicles is different in various regions or poles of the cell. (d) Epithelial cells specialized for secretion have distinct polarity, with RER abundant at their basal ends and mature secretory granules at the apical poles undergoing exocytosis into an enclosed extracellular compartment, the lumen of a gland.

cytoskeleton

a complex array of (1) microtubules, (2) microfilaments (also called actin filaments), and (3) intermediate filaments. These protein polymers determine the shapes of cells, play an important role in the movements of organelles and cytoplasmic vesicles, and also allow the movement of entire cells.

Keratins (Gr. keras, horn) or cytokeratins

a diverse family of acidic and basic isoforms that compose heterodimer subunits of intermediate filaments in all epithelial cells. Intermediate filaments of keratins form large bundles (tonofibrils) that attach to certain junctions between epithelial cells (Figure 2-27). In skin epidermal cells, cytokeratins accumulate during differentiation in the process of keratinization, producing an outer layer of nonliving cells that reduces dehydration.

Lamins

a family of seven isoforms present in the cell nucleus, where they form a structural framework called the nuclear lamina just inside the nuclear envelope (see Chapter 3).

signal transduction

activating a series of intermediary enzymes downstream to produce changes in the cytoplasm, the nucleus, or both

cytoplasmic dyneins

carry material along microtubules in the opposite direction (retrograde transport), generally toward the nucleus.

heterolysosome (or a secondary)

composite, active organelle formed by the fusing of a phagosome/pinocytotic vesicle with a lysosome

Cytoplasmic inclusions

contain accumulated metabolites or other substances, but unlike organelles have little or no metabolic activity themselves. Most inclusions are transitory structures not enclosed by membrane. Lipid droplets, accumulations of lipid filling adipocytes (fat cells) and present in various other cells, Glycogen granules, aggregates of the carbohydrate polymer in which glucose is stored, visible as irregular clumps of periodic acid-Schiff (PAS)—positive or electron-dense material in several cell types, notably liver cells, and Pigmented deposits of naturally colored material, including melanin, dark brown granules which in skin serve to protect cells from ultraviolet radiation; lipofuscin, a pale brown granule found in many cells, especially in stable nondividing cells (eg, neurons, cardiac muscle), containing a complex mix of material partly derived from residual bodies after lysosomal digestion; and hemosiderin, a dense brown aggregate of denatured ferritin proteins with many atoms of bound iron, prominent in phagocytic cells of the liver and spleen, where it results from phagocytosis of red blood cells Inclusions are cytoplasmic structures or deposits filled with stored macromolecules and are not present in all cells. (a) Lipid droplets are abundant in cells of the adrenal cortex and appear with the TEM as small spherical structures with homogenous matrices (L). Mitochondria are also seen here. As aggregates of hydrophobic lipid molecules these inclusions are enclosed by a single monolayer of phospholipids with various peripheral proteins, including enzymes for lipid metabolism. In routine processing of tissue for paraffin sections, fat droplets are generally removed, leaving empty spaces in the cells. Common fat cells have cytoplasm essentially filled with one large lipid droplet. (X19,000) (b) TEM of a liver cell cytoplasm shows numerous individual or clustered electron-dense particles representing glycogen granules, although these granules lack membrane. Glycogen granules usually form characteristic aggregates such as those shown. Glycogen is a ready source of energy, and such granules are often abundant in cells with high metabolic activity. (X30,000) (c) Pigment deposits (PD) occur in many cell types and may contain various complex substances, such as lipofuscin or melanin. Lipofuscin granules represent an accumulating by-product of lysosomal digestion in long-lived cells, but melanin granules serve to protect cell nuclei from damage to DNA caused by light. Many cells contain pigmented deposits of hemosiderin granules containing the protein ferritin, which forms a storage complex for iron. Hemosiderin granules are very electron dense, but with the light microscope they appear brownish and resemble lipofuscin. The liver cells shown have large cytoplasmic regions filled with pigment deposits, which probably represent iron-containing hemosiderin. (X400; Giemsa) MEDICAL APPLICATION A condition termed hemosiderosis, in which the iron-containing inclusion hemosiderin occurs in cells of organs throughout the body, may be seen with increased uptake of dietary iron, impaired iron utilization, or with excessive lysis of red blood cells. Hemosiderosis itself does not damage cell or organ function. However, extreme accumulations of iron in cellular hemosiderin can lead to disorders such as hemochromatosis and iron overload syndrome, in which tissues of the liver and other organs are damaged.

Interactions between F-actin and myosins

form the basis for various cell movements: Transport of organelles, vesicles, and granules in the process of cytoplasmic streaming Contractile rings of microfilaments with myosin II constricting to produce two cells by cytokinesis during mitosis Membrane-associated molecules of myosin I whose movements along microfilaments produce the cell surface changes during endocytosis

receptor mediated endocytosis

integral membrane proteins (receptors) bind substances (ex lipoproteins and hormones) at the cell surface. these proteins aggregate in special membrane regions that then invaginate and pinch off internally as vesicles.

glycolipids

lipids that include oligosaccharide chains that extend outward from the cell surface and contribute to a delicate cell surface coating called the glycocalyx

cristae

long folds in the inner membrane which increase membranes surface area

transport vesicles

move material from the RER cistern to the golgi and are transported along cytoskeletal polymers by motor proteins. The transport vesicles merge with the Golgi-receiving region, or cis face.

new mitochondria

originate by growth and division (fission) of preexisting mitochondria. During cell mitosis each daughter cell receives approximately half the mitochondria in the parent cell.

Oxidases

oxidize substrates by removing hydrogen atoms that are transferred to molecular oxygen (O2), producing H2O2.

receptors

participate in important interactions such as cell adhesion, cell recognition, and the response to protein hormones

integrins

plasma membrane proteins, linked to both the cytoskeleton and ECM, allow continuous exchange of info between the cytoplasm and material in the ECM.

coat protein COP-I

promote Forward movement of vesicles in the cis Golgi network of saccules

Carrier/pump

transmembrane proteins that bind small molecules and translocate them across the membrane (protein changes shape to do this)

ER-associated degradation (ERAD)

unsalvageable proteins are translocated back into the cytosol, conjugated to ubiquitin, and then degraded by proteasomes.

coated pits

regions of the cell membrane specialized in receptor-mediated endocytosis. Their cytoplasmic surface is coated with a bristlelike structure made of clathrin.

Proteasomes

very small abundant protein complexes not associated with membrane, each approximately the size of the small ribosomal subunit. They function to degrade denatured or otherwise nonfunctional polypeptides. Proteasomes also remove proteins no longer needed by the cell and provide an important mechanism for restricting activity of a specific protein to a certain window of time. Whereas lysosomes digest organelles or membranes by autophagy, proteasomes deal primarily with free proteins as individual molecules.proteasome is a cylindrical structure made of four stacked rings, each composed of seven proteins including proteases. At each end of the cylinder is a regulatory particle that contains ATPase and recognizes proteins with attached molecules of ubiquitin. MEDICAL APPLICATION Failure of proteasomes or other aspects of a cell's protein quality control can allow large aggregates of protein to accumulate in affected cells. Such aggregates may adsorb other macromolecules to them and damage or kill cells. Aggregates released from dead cells can accumulate in the extracellular matrix of the tissue. In the brain this can interfere directly with cell function and lead to neurodegeneration. Alzheimer disease and Huntington disease are two neurologic disorders caused initially by such protein aggregates.

residual body

where indigestible material is retained

pinocytosis

("cell drinking") -involves smaller invaginations of the cell membrane which entrap extracellular fluid and its dissolved contents. -The resulting vesicles then pinch off inwardly from the cell surface and either fuse with lysosomes or move to the opposite cell surface where they fuse with the membrane and release their contents outside the cell.

phagocytosis

("cell eating") -the ingestion of particles such as bacteria or dead cell remnants. -Certain blood-derived cells, such as macrophages and neutrophils, are specialized for this activity.

Channel-linked receptors

-open associated channels upon ligand binding -promote transfer of molecules or ions across the membrane.

mitochondiral structure and ATP formation

(a) The two mitochondrial membranes and the innermost matrix can be seen in the TEM and diagram. The outer membrane is smooth and the inner membrane has many sharp folds called cristae that increase its surface area greatly. The matrix is a gel with a high concentration of enzymes. (b) Metabolites such as pyruvate and fatty acids enter mitochondria via membrane porins and are converted to acetyl CoA by matrix enzymes of the citric acid cycle (or Krebs cycle), yielding some ATP and NADH (nicotinamide adenine dinucleotide), a major source of electrons for the electron-transport chain. The movement of electrons through the protein complexes of the inner membrane's electron-transport system is accompanied by the directed movement of protons (H+) from the matrix into the intermembranous space, producing an electrochemical gradient across the membrane. Other membrane-associated proteins make up the ATP synthase systems, each of which forms a globular complex on a stalk-like structure projecting from the matrix side of the inner membrane. A channel in this enzyme complex allows proton flow down the electrochemical gradient and across the membrane back into the matrix. The flow of protons causes rapid spinning of specific polypeptides in the globular ATP synthase complex, converting the energy of proton flow into mechanical energy, which other subunit proteins store in the new phosphate bond of ATP.

plasma membrane

(cell membrane or plasmalemma) functions as a selective barrier regulating the passage of materials into and out of the cell and facilitating the transport of specific molecules. keeps ion content of cytoplasm constant.

exocytosis

-Movement of large molecules from inside to outside the cell -a cytoplasmic vesicle fuses with the plasma membrane, resulting in the release of its contents into the extracellular space -Exocytosis is triggered in many cells by transient increase in cytosolic Ca2+. Exocytosis of macromolecules made by cells occurs via either of two pathways: -Constitutive secretion: used for products that are released from cells continuously, as soon as synthesis is complete, such as collagen subunits for the ECM. -Regulated secretion: occurs in response to signals coming to the cells, such as the release of digestive enzymes from pancreatic cells in response to specific stimuli.

3 major types of Endocytosis

-Phagocytosis -Pinocytosis -Receptor-mediated endocytosis

multivesicular bodies

-formed by accumulation of small vesicles by further invaginations of the limiting membrane -may merge with lysosomes for selective degradation of their content -may also fuse with the plasma membrane and release the intralumenal vesicles outside the cell.

juxtacrine signaling

-important in early embryonic tissue interactions -signaling molecules are cell membrane-bound proteins which bind surface receptors of the target cell when the two cells make direct physical contact.

Smooth Endoplasmic Reticulum

-lack bound polyribosomes -continuous with RER but frequently less abundant -Lacking polyribosomes, SER is not basophilic and is best seen with the TEM

Endoplasmic Reticulum

-network that extends from the surface of the nucleus throughout most of the cytoplasm -encloses a series of intercommunicating channels called cisternae. (a) RER is the site for synthesis of most membrane-bound proteins three diverse activities are associated with smooth ER: (1) lipid biosynthesis, (2) detoxification of potentially harmful compounds, and (3) sequestration of Ca++ ions. Specific cell types with well-developed SER are usually specialized for one of these functions. (b) By TEM cisternae of RER appear separated, but they actually form a continuous channel or compartment in the cytoplasm. The interconnected membranous cisternae of RER are flattened, while those of SER are frequently tubular. (c) In a very thin cultured endothelial cell, both ER (green) and mitochondria (orange) can be visualized with vital fluorescent dyes that are sequestered specifically into those organelles. This staining method with intact cells clearly reveals the continuous, lacelike ER present in all regions of the cytoplasm.

rough endoplasmic reticulum

-prominent in cells specialized for protein secretion -ex: pancreatic acinar cells (making digestive enzymes), fibroblasts (collagen), and plasma cells (immunoglobulins). -The presence of polyribosomes on the cytosolic surface of the RER confers basophilic staining properties on this organelle when viewed with the light microscope. -major function is production of membrane-associated proteins, proteins of many membranous organelles, and proteins to be secreted by exocytosis.

exosomes

-small vesicles released by multi vesicular bodies -can fuse with other cells, transferring their contents and membranes

lipid rafts

-specialized membrane patches with higher concentrations of cholesterol and saturated fatty acids -reduce lipid fluidity

Diffusion

-transports small, nonpolar molecules directly through the lipid bilayer. Lipophilic (fat-soluble) molecules diffuse through membranes readily, water very slowly.

receptors

Cells also use about 25 families of receptors to detect and respond to various extracellular molecules and physical stimuli

synaptic signaling

a special kind of paracrine interaction, neurotransmitters act on adjacent cells through synapses

polyribosomes, or polysomes

During protein synthesis many ribosomes typically bind the same strand of mRNA to form larger complexes called polyribosomes, or polysomes Free polyribosomes (not attached to the endoplasmic reticulum, or ER) synthesize cytosolic and cytoskeletal proteins and proteins for import into the nucleus, mitochondria, and peroxisomes. Proteins that are to be incorporated into membranes, stored in lysosomes, or eventually secreted from the cell are made on polysomes attached to the membranes of ER. The proteins produced by these ribosomes are segregated during translation into the interior of the ER's membrane cisternae. In both pathways misfolded proteins are conjugated to ubiquitin and targeted for proteasomal degradation.

electron-transport chain

Enzymes and other components of this chain are embedded in the inner membrane and allow oxidative phosphorylation, which produces most of the ATP in animal cells.

SER 3 main functions

Enzymes in the SER perform synthesis of phospholipids and steroids, major constituents of cellular membranes. These lipids are then transferred from the SER to other membranes by lateral diffusion into adjacent membranes, by phospholipid transfer proteins, or by vesicles which detach from the SER for movement along the cytoskeleton and fusion with other membranous organelles. In cells that secrete steroid hormones (eg, cells of the adrenal cortex), SER occupies a large portion of the cytoplasm. Other SER enzymes, including those of the cytochrome P450 family, allow detoxification of potentially harmful exogenous molecules such as alcohol, barbiturates, and other drugs. In liver cells these enzymes also process endogenous molecules such as the components of bile. SER vesicles are also responsible for sequestration and controlled release of Ca2+, which is part of the rapid response of cells to various stimuli. This function is particularly well developed in striated muscle cells, where the SER has an important role in the contraction process and assumes a specialized form called the sarcoplasmic reticulum (see Chapter 10

SER MA

MEDICAL APPLICATION Jaundice denotes a yellowish discoloration of the skin and is caused by accumulation in extracellular fluid of bilirubin and other pigmented compounds, which are normally metabolized by SER enzymes in cells of the liver and excreted as bile. A frequent cause of jaundice in newborn infants is an underdeveloped state of SER in liver cells, with failure of bilirubin to be converted to a form that can be readily excreted.

receptor MA

MEDICAL APPLICATION Many diseases are caused by defective receptors. For example, pseudohypoparathyroidism and one type of dwarfism are caused by nonfunctioning parathyroid and growth hormone receptors, respectively. In these two conditions the glands produce the respective hormones, but the target cells cannot respond because they lack normal receptors.

ERAD MA

MEDICAL APPLICATION Quality control during protein production in the RER and properly functioning ERAD to dispose of defective proteins are extremely important and several inherited diseases result from malfunctions in this system. For example, in some forms of osteogenesis imperfecta bone cells synthesize and secrete defective procollagen molecules which cannot assemble properly and produce very weak bone tissue.

phospholipids

Membrane phospholipids are amphipathic (non polar and polar), polar heads towards the outside, non polar tails toward the inside. layer contains cholesterol which modulates fluidity

membrane proteins

Membrane proteins serve as receptors for various signals coming from outside cells, as parts of intercellular connections, and as selective gateways for molecules entering the cell. Transmembrane proteins often have multiple hydrophobic regions buried within the lipid bilayer to produce a channel or other active site for specific transfer of substances through the membrane.

axonemes

Microtubules are also organized into larger, more stable arrays called axonemes in the cytoplasmic extensions called cilia (discussed in Chapter 4) and flagella.

membrane trafficking

Portions of the cell membrane become part of the endocytotic vesicles or vacuoles during endocytosis; during exocytosis, membrane is returned to the cell surface.

3 major types of receptors

Protein and most small ligands are hydrophilic molecules that bind transmembrane protein receptors to initiate changes in the target cell. (a) Channel-linked receptors bind ligands such as neurotransmitters and open to allow influx of specific ions. (b) Enzymatic receptors are usually protein kinases that are activated to phosphorylate (and usually activate) other proteins upon ligand binding. (c) G-protein-coupled receptors bind ligand, changing the conformation of its G-protein subunit, allowing it to bind GTP, and activating and releasing this protein to in turn activate other proteins such as ion channels and adenyl cyclase.

protein synthesis

Protein synthesis begins on polyribosomes in the cytosol. The 5′ ends of mRNAs for proteins destined to be segregated in the ER encode an N-terminal signal sequence of 15-40 amino acids that includes a series of six or more hydrophobic residues. As shown in Figure 2-11, the newly translated signal sequence is bound by a protein complex called the signal-recognition particle (SRP), which inhibits further polypeptide elongation. The SRP-ribosome-nascent peptide complex binds to SRP receptors on the ER membrane. SRP then releases the signal sequence, allowing translation to continue with the nascent polypeptide chain transferred to a translocator complex (also called a translocon) through the ER membrane (Figure 2-11). Inside the lumen of the RER, the signal sequence is removed by an enzyme, signal peptidase. With the ribosome docked at the ER surface, translation continues with the growing polypeptide pushing itself while chaperones and other proteins serve to "pull" the nascent polypeptide through the translocator complex. Upon release from the ribosome, posttranslational modifications and proper folding of the polypeptide continue.

zymogen granules.

Secretory granules with dense contents of digestive enzymes

endosomal compartment

a dynamic collection in the peripheral cytoplasm of membranous tubules and vacuoles

autophagy

a process in which excess/nonfunctional organelles are removed. A membrane from SER forms around the organelle or cytoplasmic portion to be removed, producing an autophagosome. These then fuse with lysosomes for digestion of the enclosed material. Autophagy is enhanced in secretory cells that have accumulated excess secretory granules and in times of nutrient stress, such as starvation. Digested products from autophagosomes are reused in the cytoplasm. Autophagy is a process in which the cell uses lysosomes to dispose of excess or nonfunctioning organelles or membranes. Membrane that appears to emerge from the SER encloses the organelles to be destroyed, forming an autophagosome that then fuses with a lysosome for digestion of the contents. In this TEM the two autophagosomes at the upper left contain portions of RER more electron dense than the neighboring normal RER and one near the center contains what may be mitochondrial membranes plus RER. Also shown is a vesicle with features of a residual body MEDICAL APPLICATION Diseases categorized as lysosomal storage disorders stem from defects in one or more of the digestive enzymes present in lysosomes, usually due to a mutation leading to a deficiency of one of the enzymes, or defects due to faulty posttranslational processing. In cells that must digest the substrate of the missing or defective enzyme following autophagy, the lysosomes cannot function properly. Such cells accumulate large secondary lysosomes or residual bodies filled with the indigestible macromolecule. The accumulation of these vacuoles may eventually interfere with normal cell or tissue function, producing symptoms of the disease. A few lysosomal storage diseases are listed in Table 2-3, with the enzyme involved for each and the tissue affected.

cisternae

a series of intercommunicating channels

Ribosomes

assemble polypeptides from amino acids on molecules of transfer RNA (tRNA) in a sequence specified by mRNA. -has two subunits (large and small) bound to a strand of mRNA. The rRNA molecules in the ribosomal subunits not only provide structural support but also position transfer RNAs (tRNA) molecules bearing amino acids in the correct "reading frame" and catalyze the formation of the peptide bonds. The more peripheral proteins of the ribosome seem to function primarily to stabilize the catalytic RNA core. These ribosomal proteins are themselves synthesized in cytoplasmic ribosomes, but are then imported to the nucleus where they associate with newly synthesized rRNA. The ribosomal subunits thus formed then move from the nucleus to the cytoplasm where they are reused many times, for translation of any mRNA strand.

peripheral proteins

bound to one of the two membrane surfaces, particularly on the cytoplasmic side. extracted with salt solutions

kinesins

carry material away from the MTOC near the nucleus toward the plus end of microtubules (anterograde transport

differentiation

cells become specialized. For example, muscle cell precursors elongate into fiber-like cells containing large arrays of actin and myosin

blastomeres

cells produced by the first zygotic cellular divisions

aquaporins

channel proteins through which water molecules pass

paracrine signaling

chemical ligand diffuses in extracellular fluid but is rapidly metabolized so that its effect is only local on target cells near its source.

trans face

golgi shipping face, larger saccules or vacuoles accumulate, condense, and generate other vesicles that carry completed protein products to organelles away from the Golgi (

clathrin

protein that forms region of cell membrane into a cage-like invagination that is pinched off in the cytoplasm as a coated vesicle with the receptor-bound ligands inside.

Golgi Apparatus or Golgi complex,

completes posttranslational modifications of proteins produced in the RER and then packages and addresses these proteins to their proper destinations.The Golgi apparatus consists of many smooth membranous saccules, some vesicular, others flattened, but all containing enzymes and proteins being processed (Figure 2-13). In most cells the small Golgi complexes are located near the nucleus. The Golgi apparatus is a highly plastic, morphologically complex system of membrane vesicles and cisternae in which proteins and other molecules made in the RER undergo further modification and sorting into specific vesicles destined for different roles in the cell. (a) TEM of the Golgi apparatus provided early evidence about how this organelle functions. To the left is a cisterna of RER and close to it are many small vesicles at the cis face (CF), or receiving face, of the Golgi apparatus, merging with the first of several flattened Golgi cisternae. In the center are the characteristic flattened, curved, and stacked medial cisternae of the complex. Cytological and molecular data suggest that other transport vesicles (TV) move proteins serially through the cisternae until at the trans face (TF), or shipping region, larger condensing secretory vesicles (SV) and other vacuoles emerge to carry the modified proteins. elsewhere in the cell. Formation and fusion of the vesicles through the Golgi apparatus is controlled by specific membrane proteins. (X30,000) Inset: A small region of a Golgi apparatus in a 1-μm section from a silver-stained cell, demonstrating abundant glycoproteins within cisternae. (b) Morphological aspects of the Golgi apparatus are revealed more clearly by SEM, which shows a three-dimensional snapshot of the region between RER and the Golgi membrane compartments. Cells may have multiple Golgi apparatuses, each with the general organization shown here and typically situated near the cell nucleus. (X30,000) (c) The Golgi apparatus location can be clearly seen in intact cultured cells processed by immunocytochemistry using an antibody against golgin-97 to show the many complexes of Golgi vesicles (green), all near the nucleus, against a background of microfilaments organized as stress fibers and stained with fluorescent phalloidin (violet). Because of the abundance of lipids in its many membranes, the Golgi apparatus is difficult to visualize in typical paraffin-embedded, H&E-stained sections. In developing white blood cells with active Golgi complexes, the organelle can sometimes be seen as a faint unstained juxtanuclear region (sometimes called a "Golgi ghost") surrounded by basophilic cytoplasm.

motor proteins

control transport along microtubules

gap junctions

couple the cells and allow exchange of ions and small molecules

stress fibers

deeper parallel F-actin bundles

glycocalyx

delicate cell surface coating, provides important antigenic and functional properties to the cell surface.

embryonic stem cells

derived from inner part of the blastocyst, can turn into any type of cell

microtubule organizing centers (MTOCs)

directs polymerization of tubulins contain short assemblies of tubulin that act as nucleating sites for further polymerization

pumps

enzymes engaged in active transport, use ATP Because they consume ATP pumps they are often referred to as ATPases.

Microtubules

fine tubular structures. the protein subunit of a microtubule is a heterodimer of α and β tubulin MEDICAL APPLICATION Several inhibitory compounds used by cell biologists to study details of microtubule dynamics are also widely used in cancer chemotherapy to block activity of the mitotic spindle in rapidly growing neoplastic cells. Such drugs include vinblastine, vincristine, and paclitaxel, all of which were originally discovered as plant derivatives.

Integral proteins

incorporated directly within the lipid bilayer. extracted by using detergents to disrupt the lipids.

Mitochondria

membrane-enclosed organelles with arrays of enzymes specialized for aerobic respiration and production of adenosine triphosphate (ATP)They are highly plastic, rapidly changing shape, fusing with one another and dividing, and are moved through the cytoplasm along microtubules. Have two separated and very different membranes that together create two compartments: the innermost matrix and a narrow inter membrane space. The outer membrane is sieve-like, containing many transmembrane proteins called porins that form channels through which small molecules such as pyruvate and other metabolites readily pass from the cytoplasm to the intermembrane space. (a) In certain sectioned cells stained with H&E, mitochondria appear throughout the cytoplasm as numerous eosinophilic structures. The mitochondria usually appear round or slightly elongated and are more numerous in cytoplasmic regions with higher energy demands, such as near the cell membrane in cells undergoing much active transport. The central nuclei are also clearly seen in these cells. (b) Entire mitochondria can be shown in cultured cells, such as the endothelial cells shown here, and often appear as the elongated structures (shown in yellow or orange here), usually arrayed in parallel along microtubules. Such preparations also show that mitochondrial shape can be quite plastic and variable. Specific mitochondrial staining such as that shown here involves incubating living cells with specific fluorescent compounds that are specifically sequestered into these organelles, followed by fixation and immunocytochemical staining of the microtubules. In this preparation, microtubules are stained green and mitochondria appear yellow or orange, depending on their association with the green microtubules. The cell nucleus was stained with DAPI (4′,6-diamidino-2-phenylindole). MEDICAL APPLICATION Myoclonic epilepsy with ragged red fibers (MERRF) is a rare disease occurring in individuals in whom cells of specific tissues, notably regions of skeletal muscle, inherit mitochondrial DNA with a mutated gene for lysine-tRNA, leading to defective synthesis of respiratory chain proteins which can produce structural abnormality in muscle fibers and other cells.

Channels

multipass proteins forming transmembrane pores through which ions or small molecules pass selectively.

Microfilaments (Actin Filaments)

omposed of actin subunits and allow motility and most contractile activity in cells, using reversible assembly of the actin filaments and interactions between these filaments and associated myosin family proteins. (a) Actin filaments or microfilaments are helical two-stranded polymers assembled from globular actin subunits. (b) Assembly of actin filaments (F-actin) is polarized, with G-actin subunits added to the plus (+) end and removed at the minus (-) end. Even actin filaments of a constant length are highly dynamic structures, balancing G-actin assembly and disassembly at the opposite ends, with a net movement or flow along the polymer known as treadmilling.

secretory granules

originate as condensing vesicles in the golgi apparatus, found in cells that store a product until its release by exocytosis is signaled by a metabolic, hormonal, or neural message (regulated secretion). are surrounded by membrane and contain a concentrated form of the secretory product TEM of one area of a pancreatic acinar cell shows numerous mature, electron-dense secretory granules (S) in association with condensing vacuoles (C) of the Golgi apparatus (G). Such granules form as the contents of the Golgi vacuoles become more condensed. In H&E-stained sections secretory granules are often shown as intensely eosinophilic structures, which in polarized epithelial cells are concentrated at the apical region prior to exocytosis. (X18,900)

multipass proteins

polypeptide chains of many integral proteins, span the membrane several times.

apoptosis

process in which the protein cytochrome c is released from the inner membrane's electron transport chain. In the cytoplasm this protein activates sets of proteases that degrade all cellular components. results in rapid cell death.

lipofuscin granules

residual bodies can accumulate as granules

COP-I

retrograde movements

endocrine signaling

signal molecules (hormones) are carried in the blood from their sources to target cells throughout the body.

autocrine signaling

signals bind receptors on the same cells that produced the messenger molecule.

Transmembrane Proteins & Membrane Transport

simple diffusion-lipophilic and small uncharged molecules (a). channels (multipass proteins) -ions (b) carriers/pumps (change shape)-larger, water-soluble molecules (c) Diffusion, channels and most carrier proteins translocate substances across membranes using only kinetic energy. In contrast, pumps are carrier proteins for active transport of ions or other solutes and require energy derived from ATP.

Lysosomes

sites of intracellular digestion and turnover of cellular components,are membrane-limited vesicles that contain about 40 different hydrolytic enzymes and are particularly abundant in cells with great phagocytic activity (eg, macrophages, neutrophils). lysosomal enzymes are capable of breaking down most macromolecules.usually spherical, range in diameter from 0.05 to 0.5 μm and present a uniformly granular, electron-dense appearance in the TEM Lysosomes are spherical membrane-enclosed vesicles that function as sites of intracellular digestion and are particularly numerous in cells active after the various types of endocytosis. Lysosomes are not well shown on H&E-stained cells but can be visualized by light microscopy after staining with toluidine blue. (a) Cells in a kidney tubule show numerous purple lysosomes (L) in the cytoplasmic area between the basally located nuclei (N) and apical ends of the cells at the center of the tubule. Using endocytosis, these cells actively take up small proteins in the lumen of the tubule, degrade the proteins in lysosomes, and then release the resulting amino acids for reuse. (X300) (b) Lysosomes in cultured vascular endothelial cells can be specifically stained using fluorescent dyes sequestered into these organelles (green), which are abundant around the blue Hoechst-stained nucleus. Mitochondria (red) are scattered among the lysosomes. (c) In the TEM lysosomes (L) have a characteristic very electron-dense appearance and are shown here near groups of Golgi cisternae (G). The less electron-dense lysosomes represent heterolysosomes in which digestion of the contents is under way. The cell is a macrophage with numerous fine cytoplasmic extensions (arrows). (X15,000) Cytosolic components are protected from these enzymes by the membrane surrounding lysosomes and because the enzymes have optimal activity at an acidic pH (~5.0). Any leaked lysosomal enzymes are practically inactive at the pH of cytosol (~7.2) and harmless to the cell. Material taken from outside the cell by endocytosis is digested when the membrane of the phagosome or pinocytotic vesicle fuses with a lysosome.

Rab proteins

small GTPases that bind guanine nucleotides and associated proteins. Direct Vesicle trafficking through the endosomal compartment

Peroxisomes

spherical organelles enclosed by a single membrane and named for their enzymes producing and degrading hydrogen peroxide, H2O2 Peroxisomes are small spherical, membranous organelles, containing enzymes that use O2 to remove hydrogen atoms from fatty acids, in a reaction that produces hydrogen peroxide (H2O2) that must be broken down to water and O2 by another enzyme, catalase. (a) By TEM peroxisomes (P) generally show a matrix of moderate electron density. Aggregated electron-dense particles represent glycogen (G). (X30,000) (b) Peroxisomes (P) in most species are characterized by a central, more electron-dense crystalloid aggregate of constituent enzymes, as shown here. (X60,000) (c) A cultured endothelial cell processed by immunocytochemistry shows many peroxisomes (green) distributed throughout the cytoplasm among the vitally stained elongate mitochondria (red) around the DAPI-stained nucleus (blue). Peroxisomes shown here were specifically stained using an antibody against the membrane protein PMP70. Peroxisomes form in two ways: budding of precursor vesicles from the ER or growth and division of preexisting peroxisomes. Peroxisomal proteins are synthesized on free polyribosomes and have targeting sequences of amino acids at either terminus recognized by receptors located in the peroxisomal membrane for import into the organelle. MEDICAL APPLICATION Several fairly rare disorders arise from defective peroxisomal proteins. Neonatal adrenoleukodystrophy is caused by a defective integral membrane protein needed for transport of very-long-chain fatty acids into the peroxisome for β-oxidation. Accumulation of these fatty acids in body fluids can disrupt the myelin sheaths in nerve tissue, causing severe neurologic symptoms. Deficiencies of peroxisomal enzymes cause Zellweger syndrome that affects the structure and functions of several organ systems.

Peroxidases

such as catalase immediately break down H2O2, which is potentially damaging to the cell. These enzymes also inactivate various potentially toxic molecules, including some prescription drugs, particularly in the large and abundant peroxisomes of liver and kidney cells.

Actin-binding proteins

such as formin and others just mentioned, change the dynamic physical properties of microfilaments, particularly their lengths and interactions with other structures, and this determines the viscosity and other mechanical properties of the local cytoplasm.

G protein-coupled receptors

upon ligand binding they stimulate associated G proteins which then bind the guanine nucleotide GTP and are released to activate other cytoplasmic proteins.