TheCell7e Ch13 Lecture

The Cytoskeleton and Cell Movement

Overview

• 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.

Functions of the Cytoskeleton

• 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.

Types of Cytoskeletal Filaments

1. 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.

2. 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.

3. 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.

Detailed Examination of Actin Filaments

Structure and Organization of Actin Filaments

• 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.

Actin-Binding Proteins

• 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 Motors

Overview

• 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.

Muscle Contraction Mechanism

• 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.

Non-Muscle Myosins

• Serve various functions including transporting vesicles and organelles.

• Myosin I and Myosin V are involved in cargo transport along actin filaments.

Microtubules and Their Role in Cell Movement

Structure and Dynamics

• 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.

Microtubule-Associated Proteins (MAPs)

• Regulate dynamic stability and interactions of microtubules with other cellular structures.

• Drugs like colchicine inhibit polymerization, while paclitaxel stabilizes microtubules to block cell division.

Motor Proteins

• Kinesins: Move toward the plus end. Kinesin I primarily transports vesicles.

• Dyneins: Move toward the minus end, involved in transporting organelles and vesicle recycling.

Intermediate Filaments

Structure and Function

• Provide mechanical strength and structural support within cells.

• Composed of various proteins including keratins in epithelial cells and vimentin in fibroblasts.

Role in Cell Mechanics

• Attach to desmosomes and hemidesmosomes to maintain cell integrity.

• Intermediate filaments exhibit stability and do not undergo rapid assembly/disassembly like microtubules.

Clinical Significance

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