Cytoskeleton and Cell Motility Notes

The cytoskeleton is a network of protein filaments found throughout the cytoplasm.
It provides the cell with its shape, offers support, and facilitates movement.
Major components include microtubules, intermediate filaments, and actin filaments.

The cytoskeleton functions as:

A dynamic scaffold: Provides structural support, determines cell shape, and resists deformation.
An internal framework: Positions organelles within the cell.
A network of tracks: Directs the movement of materials and organelles within cells (e.g., mRNA delivery).
A force-generating apparatus: Moves cells from one place to another (e.g., sperm, white blood cells, fibroblasts).
An essential component of cell division machinery: Separates chromosomes during mitosis and meiosis and splits the parent cell during cytokinesis.

Epithelial cells: Microtubules for support and organelle transport, intermediate filaments for structural support, and microfilaments for supporting microvilli.
Neurons: Microtubules for support and organelle transport, intermediate filaments for structural support, and microfilaments for neuronal elongation.
Dividing cells: Microtubules form the mitotic spindle, intermediate filaments provide structural support, and microfilaments are involved in cell division.

Long, relatively stiff, hollow tubes of protein.
Play a critical organizing role in all eukaryotic cells.
Can rapidly disassemble in one location and reassemble in another.
Usually grow out from an organizing center called the centrosome.
Form a system of tracks for the transport of vesicles, organelles, and other cell components.
Can form stable structures like cilia and flagella.

Hollow tubes made of globular tubulin subunits.
Tubulin is a dimer composed of α-tubulin and β-tubulin.
Found in the cytoskeleton, mitotic spindle, centrioles, and the core of cilia and flagella.
Function in cell support and movement of materials (e.g., between the cell body and axon terminals of a neuron).

The major microtubule-organizing center.
Consists of a pair of centrioles surrounded by a matrix of proteins.
The centrosome matrix includes γ-tubulin ring complexes, which serve as nucleation sites for microtubule growth.
The minus end of each microtubule is embedded in the centrosome, while the plus end extends into the cytoplasm.

Microtubules grow and shrink independently of their neighbors.
New microtubules grow (red arrows), and old microtubules shrink (blue arrows).
Microtubules can shrink partially and then start growing again, or disappear completely.
A newly formed microtubule will persist only if both its ends are protected from depolymerization.
Minus ends are generally protected by organizing centers.
Plus ends can be stabilized by binding to specific proteins (capping proteins).
Selective stabilization of microtubules can polarize a cell.

GTP hydrolysis controls the dynamic instability of microtubules.
Tubulin dimers carrying GTP (red) bind more tightly to one another than do tubulin dimers carrying GDP (dark green).
The rapidly growing plus ends of microtubules, capped by newly added GTP-tubulin, tend to keep growing.
If microtubule growth is slow, GTP may be hydrolyzed to GDP before fresh dimers loaded with GTP bind.
The GTP cap is lost, and GDP-carrying dimers are less tightly bound, causing the protofilaments to peel away from the plus end, leading to microtubule shrinkage.

Colchicine: Binds tightly to free tubulin dimers and prevents their polymerization into microtubules.
Taxol: Binds tightly to microtubules and prevents them from losing subunits.
Both colchicine and Taxol arrest dividing cells in mitosis and are used to treat human cancers.

Most differentiated animal cells are polarized.
Microtubules guide the transport of organelles, vesicles, and macromolecules in both directions along a nerve cell axon.
All of the microtubules in the axon point in the same direction, with their plus ends toward the axon terminal.
Oriented microtubules serve as tracks for the directional transport of materials.
Outward traffic (red circles) is driven by one set of motor proteins, and reverse traffic (blue circles) is driven by another set of motor proteins.

Motor proteins move along cytoplasmic microtubules.
Two families: kinesins and dyneins.
Kinesins: Generally move toward the plus end of a microtubule (outward from the cell body).
Dyneins: Move toward the minus end (toward the cell body).
Kinesins and cytoplasmic dyneins are generally dimers with two globular ATP-binding heads and a single tail.
Motor proteins move along microtubules using their globular heads that have ATPase activity.

Motor proteins use the energy of ATP hydrolysis to move in one direction along the filament.
The heads of kinesin and cytoplasmic dynein interact with microtubules in a stereospecific manner.
The tail of a motor protein binds to some cell component (e.g., a vesicle or an organelle) and determines the type of cargo that the motor protein can transport.
Transport toward the plus end of a microtubule is carried out by different types of kinesin motors.
Transport toward the minus end is mediated by cytoplasmic dynein.
Motor proteins convert chemical energy (stored in ATP) into mechanical energy.

Move along microtubule (MT) filaments and are powered by the hydrolysis of adenosine triphosphate (ATP).
Kinesin-1 is essential for the transport of mitochondria, endoplasmic reticulum- and Golgi-derived vesicles, messenger RNAs.

Discovered as the protein responsible for the movement of cilia and flagella.
Two well-studied roles:
- As a force-generating agent in positioning the spindle and moving chromosomes during mitosis.
- As a minus end–directed microtubular motor with a role in positioning the centrosome and Golgi complex and moving organelles, vesicles, and particles through the cytoplasm.
Contains two dynein heavy chains and a number of smaller intermediate and light chains.
Each dynein heavy chain contains a large, globular, force‐generating head, a protruding stalk containing a binding site for the microtubule, and a stem.

Microtubules and motor proteins position organelles within a eukaryotic cell.
The ER extends out from its points of connection with the nuclear envelope along microtubules.
Kinesins attached to the outside of the ER membrane pull the ER outward along microtubules.
Cytoplasmic dyneins attached to the Golgi membranes pull the Golgi apparatus inward toward the nucleus.

Many hairlike cilia project from the surface of epithelial cells that line the human respiratory tract.
A cilium beats by performing a repetitive cycle of movements, consisting of a power stroke followed by a recovery stroke.
Flagella propel a cell through fluid using repetitive wavelike motion.
Microtubules in a cilium or flagellum are arranged in a “9 + 2” array.
The motor protein ciliary dynein generates the bending motion of the core.

Hereditary defects in ciliary dynein cause Kartagener’s syndrome.
Characterized by situs inversus totalis (mirror-image reversal of internal organs).
Symptoms include frequent respiratory infections, sinus infections, ear infections, and chronic nasal congestion.
Men with this disorder are infertile because their sperm are nonmotile.

Kinesins, dyneins, and myosins.
Motor proteins convert chemical energy (stored in ATP) into mechanical energy.
Kinesins and dyneins move along microtubules, whereas myosins move along actin filaments.
Motor proteins move unidirectionally along their cytoskeletal track in a stepwise manner.