The Cytoskeleton and Cell Motility

Flashcards about the cytoskeleton and cell motility

Amatoxins

Potent inhibitors of RNA polymerase II.

Phallotoxins

Poison cells by binding tightly and specifically to actin filaments of the cytoskeleton.

Colchicine

High affinity binding to tubulin, preventing microtubule assembly

Taxol

Stabilized microtubules and kept them from depolymerizing

Cytoskeleton

Composed of 3 well-defined filamentous structures forming an elaborate interactive and dynamic network; has functions analogous to that of skeleton (support cell; play key role in mediating cell movements)

Microtubules (MTs)

Long, hollow unbranched tubes with walls composed of tubulin subunits.

Microfilaments (MFs)

Solid, thinner structures composed of actin; often organized into a branching network.

Intermediate filaments (IFs)

Tough, ropelike fibers composed of a variety of related proteins.

Microtubule wall

Globular proteins arranged in longitudinal rows (protofilaments).

Plus end

Fast-growing (row of -tubulin subunits on tip).

Minus end

Slow-growing (row of - tubulin subunits on tip).

Microtubule-associated proteins (MAPs)

Increase the stability of microtubules and promote their assembly by linking tubulin subunits together making it harder for them to fall apart

Motor proteins

Convert chemical energy (stored in ATP) into mechanical energy that is used to generate force (muscle cell contraction) or to move cellular cargo attached to the motor protein

Kinesins and dyneins

Move along MTs.

Myosins

Move along MFs.

Kinesins

move vesicles/organelles from cell body to synaptic knobs along an MT track

Kinesin-1

Each kinesin-1 is a tetramer constructed of 2 identical heavy chains and 2 identical light chains

Kinesin-1

Moves along MTs toward their plus end; plus end-directed microtubular motor

Kinesin-14

A small subfamily (called kinesin-14) moves in opposite direction, toward '-' end of the microtubular track.

Kinesin-13

Binds to either end of a microtubule and bring about its depolymerization rather than moving along its length; often referred to as microtubule depolymerases

Dynein

First MT-associated motor found (1963); it was found to be responsible for moving cilia and flagella

Cytoplasmic dynein

Moves processively along MT toward polymer's minus end — opposite the movement of most kinesins

Cytoplasmic dynein

Does not interact directly with membrane-bounded cargo, but requires an intervening adaptor, most often the multisubunit protein dynactin; also reregulates dynein activity by increasing the processivity of dynein

Microtubule-organizing centers (MTOCs)

Structures where MT nucleation takes place rapidly inside a cell

Centrosomes

Contains 2 barrel-shaped centrioles surrounded by amorphous, electron dense pericentriolar material (PCM)

Centrioles

Cylindrical structures; ~0.2 µm in diameter and typically about twice as long; contain 9 evenly spaced fibrils, each of which contains 3 MTs, designated the A, B, and C tubules

Basal body

Outer MTs in cilium or flagellum are generated directly from MTs in a structure;

-tubulin

A common protein component of all MTOCs

-TuRC

A helical array of -tubulin subunits, each bound with a set of accessory proteins

+TIPs

Bind to plus-end of growing MTs

Katanin

An enzyme named after the samurai sword; it severs MTs into shorter pieces

Posttranslational modifications to the tubulin subunits

The covalent attachment of multiple glutamates onto the C-terminus of tubulin

Dynamic instability

Shrinking MTs can coexist in same cell region; a given MT can switch back and forth unpredictably (stochastically) between growing and shortening phases

Ciliopathies

Diseases caused by organelle dysfunction that all result from defects in cilia

IFT88

A key IFT protein encoded by a gene already well known in the kidney disease world

Bardet-Biedl syndrome [BBS]

A disease caused by mutations in any one of a number of genes that affect protein trafficking into cilia

Intermediate Filaments (IFs)

Strong, flexible, ropelike fibers that provide mechanical strength to cells that are subjected to physical stress, including neurons, muscle cells and epithelial cells lining lining the body's cavities

Type V IFs - lamins

Present as part of the inner lining of the nuclear envelope

Plectin

An elongated, dimeric protein that can exist in numerous isoforms; has an IF binding site at one end and depending upon isoform, a binding site for another IF, MT or MF at the other end

Keratin filaments

Constitutes the primary structural proteins of epithelial cellsincluding epidermal cells, liver hepatocytes, and pancreatic acinar cells

Neurofilaments

Filaments made of 3 distinct proteins: NF-L, NF-H and NF-M, all of the type IV group

NF-H and NF-M

Have sidearms that project outward from the NF; the sidearms are thought to maintain proper spacing between the parallel NFs of the axon

Desmin

Plays a key structural role in maintaining muscle cell myofibril alignment

Actin

The most abundant protein in most cells.

Actin filament/F-actin/microfilament

a flexible, helical filament; a two-stranded structure with 2 helical grooves running along its length

Barbed end

The fast-growing end

S1

A proteolytic fragment of myosin, called S1, used to bind tightly and "decorate" the sides of actin filaments

Pointed end

The end that looks like an arrowhead

Actins

Have been remarkably conserved during eukaryotic evolution (yeast cell and rabbit skeletal muscle actin amino acid sequences are 88% identical)

Cytochalasins

Promote MF depolymerization at the minus (pointed) end by blocking the plus (barbed) ends.

Phalloidin

Binds to intact actin filaments and prevents their turnover.

Latrunculin

Binds to free monomers and blocks their incorporation into polymer.

Myosin

All molecular motors known to interact with actin

Myosin head(motor domain)

Have a site that binds the actin filament and one that binds and hydrolyzes ATP to drive the myosin motor

Skeletal muscles

The muscle are anchored to bones that they move; they are under voluntary control and can be consciously commanded to contract

Skeletal muscle cell

Cylindrically shaped cell is typically 10-100 µm thick, >100 mm long and contains hundreds of nuclei

Sarcomeres

The repeating linear array of contractile units

Sliding Filament Model

All skeletal muscles operate by shortening

M line

The titin molecules originate here in center of each sarcomere

Tropomyosin

Elongated molecule, ~40 nm long; fits securely into grooves between 2 thin filament actin chains; each rod-shaped interacts with 7 actin subunits linearly along F-actin chain

Troponin

A globular protein complex made of 3 subunits - each has distinct, important functional role; ~40 nm apart on thin filament, contact both the actin and tropomyosin components of thin filament

Excitation-contraction coupling

The steps linking the arrival of a nerve impulse at the muscle plasma membrane to the shortening of sarcomeres deep within muscle fiber

T tubules

Folds (transverse [T] tubules) in the muscle plasma membrane

Sarcoplasmic reticulum (SR)

Forms a membranous sleeve around myofibril