TheCell7e Ch13 Lecture

The Cytoskeleton and Cell Movement

The cytoskeleton is a dynamic network of protein filaments in eukaryotic cells, providing structural support, determining shape, and facilitating movement.
Composed of three main types of protein filaments: actin filaments, microtubules, and intermediate filaments.

Structural Framework: Determines cell shape and organization of organelles.
Cell Movement: Facilitates the movement of whole cells and internal transport.
Dynamic Structure: Continuously reorganizes as cells move and change shape.

Actin Filaments (Microfilaments):
- Composed of actin, polymerized to form flexible fibers about 7 nm in diameter.
- Organized into bundles and three-dimensional networks.
- Actin-binding proteins regulate their assembly and disassembly.
Microtubules:
- Composed of tubulin dimers (alpha and beta), forming hollow tubes 25 nm in diameter.
- Essential for cell movements, providing pathways for transport within cells.
- Exhibit dynamic instability, rapidly assembling and disassembling.
Intermediate Filaments:
- Intermediate in diameter between actin filaments and microtubules.
- Provide mechanical strength and maintain cell shape.
- Diverse proteins (e.g., keratins, vimentin) depending on cell type.

Polymerization: Actin monomers (G actin) polymerize into filamentous actin (F actin) forming a helical structure.
Polarity: Actin filaments exhibit polarity, important for directionality concerning myosin movement.
Nucleation: The initial step of actin polymerization where dimers and trimers are formed before monomers are added to the filament.
Treadmilling: Growing at the barbed end while disassembling at the pointed end, illustrating the dynamic behavior of actin.

Profilin: Increases concentration of ATP-actin.
Cofilin: Severing protein that creates new filament ends available for polymerization.
Formins & Arp2/3 Complex: Initiate actin filament growth; the latter promotes branched filament networks essential in cell movement.

Myosin is a motor protein converting ATP to mechanical energy to induce movement, most notably in muscle contraction.
Skeletal Muscle Structure: Comprises bundles of muscle fibers with myofibrils containing sarcomeres.

The sliding filament model explains that myosin heads bind to actin and pull it, shortening sarcomeres during contraction.
Myosin II consists of two heavy and two light chains, where the heads interact with actin filaments.
Regulation by Calcium: Increase in cytosolic calcium activates tropomyosin and troponin allowing myosin to bind actin leading to contraction.

Composed of tubulin dimers forming rigidity in microtubules, which display dynamic assembly and disassembly.
Polarity: Microtubules have plus and minus ends, directing transport of vesicles and organelles.

Regulate dynamic stability and interactions of microtubules with other cellular structures.
Drugs like colchicine inhibit polymerization, while paclitaxel stabilizes microtubules to block cell division.

Kinesins: Move toward the plus end. Kinesin I primarily transports vesicles.
Dyneins: Move toward the minus end, involved in transporting organelles and vesicle recycling.

Provide mechanical strength and structural support within cells.
Composed of various proteins including keratins in epithelial cells and vimentin in fibroblasts.

Attach to desmosomes and hemidesmosomes to maintain cell integrity.
Intermediate filaments exhibit stability and do not undergo rapid assembly/disassembly like microtubules.

Keratin mutations can lead to skin disorders such as Epidermolysis bullosa simplex (EBS), demonstrating the critical mechanical role of intermediate filaments in tissue stability.