The Cytoskeleton

Actin is most concentrated in?

cell cortex

cytochalasins

fungal metabolites that prevent the addition of new monomers to existing MFs PREVENTS ACTIN POLYMERIZATION

intermediate filaments function

give shape and physical support to cell; anchor cells to each other and to extracellular material; compartmentalize cell contents; integral to cell junctions/cellular connectivity keratin, lamins, vimentins, etc DO NOT REQUIRE ATP/GTP hydrolysis to form PROVIDES STRUCTURAL STRENGTH TO ANIMAL CELLS TO PROVIDE STRUCTURAL INTEGRITY •More permanent than microtubules and microfilaments •Reinforce cell shape and organelle positioning •Nuclear lamina

tubulin

globular protein subunit forming the hollow cylinder of microtubules •Dimer of 55-kd polypeptides -α -tubulin (alpha) -β - tubulin (beta) •Encoded by related genes •third type of tubulin -γ-tubulin -at centrosome -has role in initiating MT assembly *Highly conserved protein (meaning it's similar across species) with subdomnains including GTP binding sites and MAP (microtubule associated proteins) binding sites.

plectin

links microtubules to intermediate filaments

thymosin

stimulates the maturation of lymphocytes into T cells of the immune system monomer sequestering protein; prevents polymerization

cytoskeletal functions

structure and support, intracellular transport, contractility and motility, spatial organization vesicle transport, neuron AP propagation,

Intermediate filaments provide strength to animal cells

without int filaments cells rupture (both the junctional complex and p. membrane --- no structural integrity)

Gamma-TuSC

γ-tubulin functions as a microtubule nucleating factor that is localized in the microtubule organizing center (the centrosome in animal cells and the spindle pole body in yeast).

Microtubule polarity

γ-tubulin makes direct contact with the α-tubulin subunit of the tubulin heterodimer establishing what? New subunits (polymerization) are added at the + end. Polarity is critical for function.

Eukaryotic Flagella (longitudinal section) Ciliary and Flagellar Axonemes

•9 + 2 MT arrangement •Dynein arms and radial spokes with attached heads occur at intervals along the longitudinal axis •central microtubules -C1 and C2 *cillia = whip like motion flagella = wave like motion BOTH of which are powered via cycles of bending and relaxation of dynein arms and stabilization / attachment of radial spokes

Endocytic Pathway

•Endocytic movement •Occurs along microtubules -Can be blocked by drugs

Axon Transported Vesicles

(EM of axonal transported vesicles and microtubules in longitudinal section) MT are VITAL in transporting vesicles -vessicles do not move unless associated with motor proteins AND MTs

Arrangements of Protofilaments

(Protofilament = A filament of polymerized tubulin in a cell, which becomes part of a microtubule quotations) •Singlet -Typical microtubule -Tube built from 13 protofilaments •Doublet -Additional set of 10 protofilaments -Forms a second tubule by fusing to the wall of a singlet •Triplet -Attachment of another 10 protofilaments (basal bodies and centrioles)

microfilaments

(sometimes called thin filaments or actin filaments) Long, thin fibers that function in the movement and support of the cell (MUCH THINNER THAN MTs) a small rodlike structure, about 4-7 nanometers in diameter, present in numbers in the cytoplasm of many eukaryotic cells. *binds ATP (ADP when in filament) *ATP binding cleft in middle of actin monomer *DYNAMIC structure ----> polymerizes 2 protofilaments into helical strucutre

Motor Mediated Transport

*Motor proteins needed for vesicle/organelle transport. *These use energy derived from ATP hydrolysis to travel along microtubules or filaments. Kinesin ( - -----> +) Dynein (+ ------> -)

Microtubules and the Mitotic Spindle

*Spindle fibers: spindle polar; astral; and kinetochore fibers. *Microtubule organizing center (MTOC) called the centrosome in animal cells.

Actin filaments allow eukaryotic cells to adopt a variety of shapes and perform a variety of functions.

*VAST ARRAY of cell structures/fxns in tissues and organs is largely due to microfilament activity a) GI microvilli b) contractile bundles c) pseudopods, phyllopodia d) contractile ring (cytokinesis of cell division)

Orientation of Cellular Microtubules:Interphase and Mitosis

*polarity is critical to MT fxn *ALL MTs emanate from Centrosomes *Location of centrosomes influences POLARITY--------> polarity directly affects/influences every fxn of Mts

cell movement

-Essentially all cell motion is tied to the movement of actin filaments, microtubules, or both -Some cells crawl using actin microfilaments -Flagella and cilia have 9 + 2 arrangement of microtubules Not like prokaryotic flagella Cilia are shorter and more numerous lamellipodium filopodium cortex

Microtubule structure

-contain 13 parallel *protofilaments* made up of *ab-tubulin heterodimers* connected "head to tail" -like actin filaments, microtubules are POLAR with a + and - end -b-tubulin has GTPase activity and whether a b-tubulin molecule contains GTP or GDP affects its stability within a microtubule arrangement of protofilaments: 1. singlet 2. doublet (cilia and flagella) 3. triplet (basal bodies, centrioles) •Long, rigid, hollow tubes •25 nm in diameter with a 15 nm lumen •Radiate from a forming structure •Polarized -plus(+) and (-) ends •Formed from tubulin -55 kD protein *Microtubules have an inherent polarity (2 ends) designated plus (+) and minus (-). *alpha/beta heterodimer *ring of 13 distinct (alpha/beta) protofilament (tubulin) subunits *tubulin molecules aligned in parallel rows

Intermediate filaments (in general)

A component of the cytoskeleton that includes all filaments intermediate in size between microtubules and microfilaments Threadlike proteins in the cell's cytoskeleton that are roughly twice as thick as microfilaments Diameter: 8-12nm (smaller than MTs (24-25nm), bigger than microfilaments (less than or equal to 8nm) ) *several protein families form strong/stable polymers that resist stretch (structural function in cell: TENSION BEARING FXN Keratin family---> most diverse intermediate protein fam ---->FXN: provide mechanical support for p. membrane where cell comes into contact with other cells or ECM -----> forms a tight weave structure around nucleus, then spread out toward p. membrane in the cell e.g. Lamins inside nucleus NO POLARITY

intermediate filaments

A component of the cytoskeleton that includes filaments intermediate in size between microtubules and microfilaments. fibrous proteins familys; keratins, lamins, vimentin found in a variety of different kinds of cells, including fibroblasts, smooth muscle cells, and white blood cells. Another type III protein, desmin, is specifically expressed in muscle cells, where it connects the Z discs of individual contractile elements. A third type III intermediate filament protein is specifically expressed in glial cells, and a fourth is expressed in neurons of the peripheral nervous system. The type IV intermediate filament proteins include the three neurofilament (NF) proteins (designated NF-L, NF-M, and NF-H for light, medium, and heavy, respectively). These proteins form the major intermediate filaments of many types of mature neurons. They are particularly abundant in the axons of motor neurons and are thought to play a critical role in supporting these long, thin processes, which can extend more than a meter in length. Another type IV protein (α-internexin) is expressed at an earlier stage of neuron development, prior to expression of the neurofilament proteins. The single type VI intermediate filament protein (nestin) is expressed even earlier during the development of neurons, in stem cells of the central nervous system. The type V intermediate filament proteins are the nuclear lamins, which are found in most eukaryotic cells. Rather than being part of the cytoskeleton, the nuclear lamins are components of the nuclear envelope (see Figure 8.3). They also differ from the other intermediate filament proteins in that they assemble to form an orthogonal meshwork underlying the nuclear membrane. Despite considerable diversity in size and amino acid sequence, the various intermediate filament proteins share a common structural organization (Figure 11.31). All of the intermediate filament proteins have a central α-helical rod domain of approximately 310 amino acids (350 amino acids in the nuclear lamins). This central rod domain is flanked by amino- and carboxy-terminal domains, which vary among the different intermediate filament proteins in size, sequence, and secondary structure. As discussed next, the α-helical rod domain plays a central role in filament assembly, while the variable head and tail domains presumably determine the specific functions of the different intermediate filament proteins.

F-actin

A fibrous protein made of a long chain of G actin molecules twisted into a helix; main protein of the thin myofilament filamentous actin; 2 intertwined actin chains

dynein

A large contractile protein forming the side-arms of microtubule doublets in cilia and flagella.

Myosin

A motor protein present in muscle fibers that aids in contraction and makes up the majority of muscle fiber

nuclear lamina

A netlike array of protein filaments lining the inner surface of the nuclear envelope; it helps maintain the shape of the nucleus. not as stable as other int. filaments but not as dramatically dynamic as MTs or microfilaments phosphorylation/dephosphorylation triggers nuclear breakdown

Cytoskeleton

A network of cytoplasmic fibers that holds the cell together, helps the cell to keep its shape, and aids in movement, cellular remodelling, maintain internal homeostasis, and cellular coordination; vital to cellular fxns depend on: actin filaments microtubules intermediate filaments (each are responsible for different aspects of cell's spatial organization and mechanical properties) Cytoskeleton allows eukaryotic cells to adopt a variety of shapes, organize their interior, and interact mechanically with their environment. essential for cellular communications

Dynamic Instability

A property of actin filaments in the cytoskeleton, characterized by rapid shortening or lengthening of individual filaments. (cycles of shrinkage and growth in microtubules; cycles of formation and breakdown of MTs) *VITAL for rapid cellular remodelling •Depolymerization / polymerization cycles •GTP is hydrolyzed faster than the addition of new subunits •Results in loss of GTP cap •Disassembly •Critical for mitosis •Colchecine - encourages depolymerization via binding tightly to beta dimers •Taxol - stabilizes MTs so that they do NOT depolymerize

axoneme

A structure found in eukaryotic cilia and flagella and responsible for their motion; composed of two central microtubules surrounded by nine doublet microtubules (9 + 2 arrangement).

centrosome

A structure in animal cells containing centrioles from which the spindle fibers develop.

Centrosome

A structure in animal cells containing centrioles from which the spindle fibers develop. •Microtubule organizing center *Tubulin polymerizes from nucleation sites on this structure SITE for the formation of ALL MTs in the cell rich in gamma tubulin

Rho family GTPases

A subgroup of the small GTPase family; activation of Rho family GTPases leads to reorganisation of the cytoskeleton as well as affecting cell adhesion, for example by influencing interactions between integrins and the actin network.

D-actin

ADP bound to Actin

rate of assembly stays _____ of GTP hydrolysis

AHEAD

T-actin

ATP bound to Actin

Axonemal Dynein

ATPase that links peripheral 9 doublets and causes bending of cilium by differential sliding of doublets hydrolyzes ATP, providing the mechanical forces that promote both cilia and flagellar movement •Arrangement of globular domains and short stocks -Attachment of outer dynein arm to A tubule of one doublet and cross- bridges to B tubule of adjacent doublet -attachment to A tubule is stable •Presence of ATP -successive formation and breakage of cross-bridges to adjacent B tubule -Leads to movement of one doublet relative to the other

Activation of GTP-binding proteins has a dramatic effect on the organization of actin filaments in fibroblasts.

Actin responds to extracellular signals. Rac and Cdc42 are both members of the Rho family of GTP binding proteins that are triggered by signals and activate actin. activated actin rapidly polymerizes

Treadmilling of actin filaments

Addition of G-actin at one end (usually + end), with loss of G-actin from the other end (usually - end) *dependent of [G-Actin]/monomer concentration and rate of ATP hydrolysis / [ATP] *DYNAMIC *intermediate [G-Actin] = fast polymerization (addition of ATP bound actin monomers) @ + end, increased ATP hydrolysis @ - end (depolymerizaton) (simultaneous ADP bound monomers leaving at - end)

GTP + beta tubulin (GTP bound) = ?

Assembly/formation of tubulin structures

Tubulin polymerizes from nucleation sites on a centrosome

Centrioles (triplets of microtubules; gamma tubulin [pericentrin]) - 2 of them lie at right angles to each other (none in plants). Cloud of weakly staining pericentriolar material.

formins

Dimeric proteins which nucleate the formation of straight, unbranched actin filaments bind ATP-actin and nucleate initial polymerization of long unbranched actin filaments promotes nucleation

lamellipodium (plural lamellipodia)

Dynamic sheetlike extension on the surface of an animal cell, especially one migrating over a surface. thin sheath like projections that forms on leading edge of moving cell driven by actin polymerization (via formation of contractile bundles); pushes the cell outward (requires: actin binding proteins and motor proteins) The ______________ is a cytoskeletal protein actin projection on the leading edge of the cell. It contains a quasi-two-dimensional actin mesh; the whole structure propels the cell across a substrate.

Tubulin polymerizes from nucleation sites on a centrosome 2

Each microtubule grows and shrinks independently of its neighbor. Intracellular tubulin levels are low. Only microtubules that form are associated with the centrosome in some way (usually at the - end). easily grown in vitro, not in vivo bc intracellular [tubulin] is LOW

what are the subunits of intermediate filaments?

Fibrous proteins; large and diverse family of proteins; incorporated into stable intermediate filaments (do not get rapid polymerizations/depolymerizations) fiber proteins are insoluble there are tissue specific forms of intermediate fil that can contain different compositions

Rapid breakdown / depolymerization occurs once?

GTP hydrolysis rates exceeds the addition of new tubulin subunits

Nucleation site for Microtubules

Gamma-TuSC

severing proteins

Involved in disassembly of filament systems 1) Microfilaments --> Gelsolin - does not require ATP - Requires Ca++ --> involved in signal mediated destruction - Binds to the (+) end --> prohibit subunit addition 2) Microtubules --> Katanin - Heterodimer - ATPase activity breaks longitudinal bonds - Localized severing at centrosome --> releasing anchored MT --> promote disassembly

thus, GTP concentration is vital in maintaining?

MT structures and MT integrity

endosome

Membrane-enclosed compartment of a eukaryotic cell through which material ingested by endocytosis passes on its way to lysosomes or can exchange cargo

MAP binding sites

Microtubule Associated Proteins

MTs and Cell Polarity

Minus ends are protected from depolymerization by the centrosome + ends are stabilized by capping proteins (MAPS). capping proteins lead to MT stability/polarity and allows for it to take shape via redistribution of MTs.

nucleating proteins

Provide a template for adding actin monomers; Arp 2/3 complex

Myosin I

Simplest type of myosin, present in all cells; consists of a single actin-binding head and a tail that can attach to other molecules or organelles.

filopodium

Slender protoplasmic projection, arising from the growth cone of an axon or a dendrite, that explores the local environment. Long, thin, actin-containing extension on the surface of an animal cell. Sometimes has an exploratory function, as in a growth cone. thin stiff projections, "feelers" that fxn in directing the cell and aiding the cell to move formed by rapid polymerization of tight parallel bundles of actin filaments lots of treadmilling occurs; organization is maintained by actin binding proteins

Nucleation

The initial stage in a phase transformation. It is evidenced by the formation of small particles (nuclei) of the new phase that are capable of growing. initial aggregate of subunits, stabilized by multiple subunit-subunit contacts permitting elongation

Myosin II

The type of myosin that produces contraction by sliding actin filaments. the protein responsible for movement of the skeletal muscles. Type of myosin that exists as a dimer with two actin-binding heads and a coiled-coil tail; can associate to form long myosin filaments.

microtubules

Thick hollow tubes that make up the cilia, flagella, and spindle fibers. tubulin protein largest microtubules are dynamic structures that undergo continual assembly and disassembly within the cell. They function both to determine cell shape and in a variety of cell movements, including some forms of cell locomotion, the intracellular transport of organelles, and the separation of chromosomes during mitosis.

Microtubule-associated proteins (MAPs)

a class of proteins that participate in the regulation of microtubule assembly and function

Microtubule Associated Proteins (MAPs)

a class of proteins that participate in the regulation of microtubule assembly and function (regulate MT dynamics in cells) Cross-linking proteins that stabilize bundles of permanent microtubules (e.g. the microtubules that run the length of nerve axons) by binding to the sides of the microtubules. •Many different proteins •Examples from neurons -tau -MAP2

G-actin

a globular subunit of F actin with an active site for binding a myosin head globular monomer

centrioles

a minute cylindrical organelle near the nucleus in animal cells, occurring in pairs and involved in the development of spindle fibers in cell division.

Orientation of Cellular Microtubules:Cilia and Flagella

basal body (cross section) resembles centrosome (basically it is a centrosome) -- a MT organizing center cells with cilia and flagella have mt organizing center at the BASAL BODY core of MTs that emanate from mt organizing center/basal body = Axoneme

What binds GTP in MTs? what cascade of events transpire when bound?

beta tubulin binds GTP form protofilament columns via Hydrolysis (GTP-->GDP) and continued polymerization/assembly

Phagocytosis and Actin

binding to host surface receptors leads to release of signals signal leads to rapid actin polymerization -assists in contraction and engulfment and formation of pseudopod (for engulfment) activates actin binding proteins in cascade fashion

profilin

binds actin subunits and speeds elongation An actin-binding protein that stimulates the assembly of actin monomers into filaments; encourages binding of ATP to G actin to promote nucleation

gelsolin

breaks actin MFs and caps the newly exposed plus ends, preventing further polymerization severs filaments and binds to plus end

intracellular transport

circulation within a cell, between organelles, ex. movement of gas molecules within the cytoplasm

microfilliaments

consist of actin filaments thinnest

axonemal

driving force cilia and flagella movements Which dynein (cytoplasmic or axonemal) assemble into heterodimers and heterotrimers?

Eukaryotic Flagella (cross section)

dynein arms in presence of ATP will move along MT

Intermediate filaments are like ropes made of long, twisted strands of protein.

few free tetramers, typically stay in polymerized states NOT AS DYNAMIC as other cytoskeletal filaments

Much of the cytoskeleton is

is dynamic (can grow, shrink, and move), but can also be static, depending on the cell's needs. dynamic filaments

Types of Intermediate filaments

keratin, vimentin, neurofilaments, nuclear lamins

filopodia

long, fingerlike extensions from growth cones of axons and dendrites binding proteins

Eukaryotic Flagella

made of microtubules composed of tubulin, 9+2 arrangement ring of 9 MT doublets attached to a basal body -- which consists of 9 MT triplets (rich in gamma tubulin)

gamma tubulin

microtubule subunit that caps and stabilizes the minus end of microtubule and leads to rapid addition of subunits (MT assembly) Type of tubulin that, along with associated proteins, forms a ring complex from which microtubules are nucleated within cells

Cytoskeletal motor proteins

molecular motors such as myosins, kinesins and dyneins

lamins revisited

nuclear lamina

Tubulin polymerizes from? on what? what molecule is in high concentration?

nucleation sites centrosome sites are RICH IN GAMMA TUBULIN RINGS

progeria

pathological condition of premature old age occurring in childhood results in no nuclear lamina

cross linking proteins

possess 2 or more actin binding sites and join microfilaments into three-dimensional networks

Actin-related proteins (ARPs)

promote formation of branched actin filaments; encourages nucleation and elongation

spectrin

provides flexibility to change shape A fibrous protein that gives shape to an RBC plasma membrane. Cross linking proteins

what happens when there is a mutation in genes that encode cytoskeletal motor proteins?

random dispersions of vesicles/granules stay localized and cluster together

cell cortex

reinforcing mesh of cytoskeletal elements (mostly actin) under a plasma membrane Specialized layer of cytoplasm on the inner face of the plasma membrane. In animal cells, it is rich in the actin filaments that govern cell shape and drive cell movement. Actin is found throughout the cell. But it is concentrated in the cell cortex (the area around the plasma membrane). polymerized actin and free actin are both present in the meshlike network

Rac activation

results in extension of lamellipodia

Cdc42 activation

results in formation of filopodia

ATP cleft

site of ATP binding in Actin molecule

Phalloidin

stabilizes MFs and prevents their depolymerization

pericentriolar material (PCM)

surrounds centrioles. a nebulous cloud of various accessory proteins. Amorphous, electron-dense material that surrounds the centrioles in an animal cell. essentially gamma-tubulin

radial spokes

the proteins that extend from the fused doublets to the unfused central tubule within cilia and flagella; these never move--they keep the cell in tact and attached, which causes bending when other proteins move

Actin associations with myosin to form contractile structures that bind to various cell components including membranes.

utilization of Myosin I

Microfilaments: Formation and Treadmilling

variation based on cell type: alpha/beta/gamma actin T-actin D-Actin ATP Cleft longer than MTs, but typically always associate with other microfilaments (each monomer associates with approx 4 monomers

nucleation sites

where MTs begin to grow; needed in cells because it is hard to start MTs forming "from scratch"; stabilize the minus-ends of the MTs in cells

Actin filaments attach to points where the crawling cell is anchored to the extracellular matrix: interference- microscopy and fluorescent antibodies to actin.

you can see attachment points of crawling cells to matrix/substrate in image on left ALL actin dependent motor proteins are myosin family proteins

Microfilaments (actin filaments)in General

•Actin -Monomer (G actin) -Two intertwined actin chains (F actin) -7 nm in diameter *Most abundant protein (especially in muscle cells) -Very High [actin] : [myosin] in NON MUSCLE CELLS -100 ACTIN:1 MYOSIN in Nonmuscle cells *Associates with motor protein (Myosin) *Integral for cellular contraction

Orientation of Cellular Microtubules:Nerve Cells

•Axonal microtubules have - end in main cell body -polarity is governed by axonal MTs •Dendrites possess microtubules, with mixed polarities & may possess protofilaments.

microtubules (MT) (more depth)

•Cell organizing role (cytoplasmic) •Largest fiber of cytoskeleton -25 nm diameter •All cells contain MTs -Same core structure -Same motors (motor proteins) -Different associated proteins •Dynamic -Continuous remodeling •Movement -Intracellular>cellular -Cell division Functions: ciliary & flagellar movement; mitotic/meiotic chromosome movement; intracellular vesicular transport; and secretion. Cellular/intracellular movement

Microfilaments: Growth

•Dimers •Trimers •Directional (+ and - ends) - depends on monomer addition rates •F actin (once actin is incorporated into filament) •Reversible -Rate of association is dependent on monomer concentration -Rate of association is independent of monomer concentration (wrt to ATP hydrolysis rates) •Treadmilling e.g. elevated [G-actin] = fairly fast polymerization @ both ends; intermediate [G-Actin] = fast polymerization @ + end, increased ATP hydrolysis @ - end (depolymerizaton) *nucleation events results in actin polymerization (can occur at both ends), but most commonly most polymerization takes place at + end -+end = FAST GROWING - end = SLOW GROWING

Why does tubulin polymerize?

•Dimers bound to GTP form columns (protofilaments) •Column formation fueled by GTP -> GDP hydrolysis •Assembly continues as long as there is GTP in increasing concentrations •"GTP cap" at growing end (+ end) •Assembly (shows Dynamic Instability)

Tubulin Protofilaments

•Dimers polymerize to form microtubules •13 linear protofilaments -head to tail arrays of tubulin dimers -arranged in parallel -assembled around hollow core

MT Motor Proteins

•Dynein ( + -----> -) -2 to 3 heavy chains -multiple light and intermediate chains •Kinesin ( - -----> +) -2 heavy chains wound around each other in a coiled- coil structure -2 light chains -14 diff kinds- protein superfamily

Microtubule Motor Proteins

•Dynein (-) and Kinesin (+)move in opposite directions -globular heads of heavy chains bind MTs -motor domains cargo = vesicle or organelle binding domains contain ATPases --> ATP hyrdolysis powers motor and moves cargo along MTs *both proteins can be present at the same time to power each direction

Dynein Mediated Sliding of Axonemal Microtubules

•Dynein arm attaches to A subfiber of one microtubule •"walk" along B subfiber of adjacent doublet •toward minus end •moves microtubule in opposite direction •cross links broken; sliding can continue *ATP binding causes dynein to attach along the length of the doublet. *ATP hydrolysis results in dynein moving along microbules and the doublets sliding past one another. *This sliding is limited by support proteins and a bending motion occurs for the overall structure. [a MECHANICAL CELLULAR PROCESS] MTs are held in place by: Basal Body/outer sheath & Spokes

Microtubule Associated Proteins (MAPs) : MAP2

•MAP2 -neurons & brain tissue (expressed heavily) -280 kd -developmentally expressed -Cell body and dendrites of neuron -MAP 2B, 2A, 2C •All found in various cells of the CNS *Overall fxn: Stabilizes Mts in Neurons depending on cellular needs *MT binding domain is embedded in MT structure *second MT binding domain can bind other Mts and Intermediate filaments (depending on cellular needs)

MT Assembly: the Centrosome

•Microtubule organizing center •Slow-growing minus end embedded in centrosome matrix -surrounds pair of centrioles in animal cells •Matrix determines number of MTs in a cell -By nucleating growth of new MTs -Called pericentriolar material (There is one centrosome in interphase animal cells (positioned near nucleus).) *All MTs begin nucleation @ the centrosome

cytoskeleton function overview

•Network of cytoplasmic fibers •Cell motility •Support •Regulation •Intracellular transport

EM: Basal Bodies of Cilia

•Surface of epithelial cell •Contains basal bodies -Connected to ciliary microtubules Systems •Top: cilia transverse section -central mt doublet -surrounded by nine MT pairs -One of each pair has hook-like appendage *Cilia (in respiratory tract (trachea, SI) and epithelia of oviduct); flagella have same basic internal structure (in humans- sperm are flagellated).

Microtubule Associated Proteins (MAPs): Tau

•TAU -45-60 kD -Neurons •Enriched in axons •phosphorylated •TAU and Alzheimer's Disease -Neuronal cytoskeleton is progressively disrupted -Replaced by tangles of paired helical filaments (PHF) -PHFs composed mainly of hyperphosphorylated form of Tau -Mainly plus-directed transport -Organelles are unable to penetrate neurites -Leads to •stunted growth •increased susceptibility to oxidative stress •pathologic aggregation of proteins such as amyloid precursor protein -tau:tubulin ratio is normally low •increased levels of tau become detrimental

Actin-binding proteins (in green) control the behavior of microfilaments.

Actin binding proteins: thymosin, profilin, formins, actin-related proteins, spectrin, gelsolin, and filamin.

ATP Hydrolysis _____________ the stability of the actin polymer.

DECREASES

centrioles

Located near the nucleus and help to organize cell division made of gamma-tubulin (9) triplets (organized into cyclinders), inside lies centrosomes exact function wrt MT fxns is unknown; NOT NEEDED FOR NUCLEATION

zipper mechanism

actin polymerizes only immediately around bacterium or substance for engulfment

filamin

acts to "splice," joining two MFs together where they intersect An actin-binding protein that cross-links actin filaments into networks. Gel-forming protein which cross-links actin filaments at right angles to promote the formation of web-like networks with the consistency of highly viscous gels; these proteins are necessary for the formation of the lamellipodia used by cells to crawl across a solid surface