lecture 13

Cytoskeletal Microtubules & Microfilaments & Motility

• Students will be able to correlate the molecular organization of microtubules to their dynamic nature, interpret structural adaptations of microtubules (MTs) to their function, correlate motor proteins in cell trafficking to MTs, appraise the importance of microtubules as a drug target, and correlate the molecular structure of actin to its function.

Cytoskeleton

• The cytoplasm of animal cells contains a complex three-dimensional protein filament network (cytoskeleton) maintaining cell shape.
• The cytoskeleton is active in cell and organelle movement.
• It has three components: microfilaments, intermediate filaments, and microtubules.

Microtubules

• Microtubules (MTs) are long, hollow structures acting as intracellular pathways.
• Centrosomes, near the nucleus, contain y-tubulin ring complexes that nucleate microtubules.
• Microtubules are dynamic, frequently changing length by growing and shrinking at the plus end (away from nucleus). The average half-life is about 10 minutes.
• Each microtubule consists of 13 parallel protofilaments made of a- and b-tubulin heterodimers.

Functions of MTs

• Provide cell shape rigidity and maintain structure.
• Regulate organelle and vesicle movement.
• Form the basis of cilia and flagella.
• Create intracellular compartments.
• Essential for cell division (mitotic spindle).

Clinical Correlation

• Drugs like colchicine can disrupt microtubule formation, affecting leukocyte function (migration, phagocytosis) and having anti-inflammatory effects (e.g., acute gouty arthritis).

Microtubule-Associated Proteins

• Motor proteins (e.g., kinesin and dynein) move organelles and vesicles along microtubules.
• Kinesin moves toward the plus end, and dynein moves toward the minus end, both driven by ATP.

Centrioles

• Centrioles are small cylindrical structures (nine triplets) forming the microtubule organizing center (or centrosome).
• They are perpendicular to each other.
• Centrioles are important in cell division by forming the spindle apparatus, also forming cilia and flagella.

Actin Filaments (Microfilaments)

• Thin filaments (microfilaments) are composed of two intertwined chains of globular actin (G-actin).
• These form a filamentous protein (F-actin).
• Filaments have a plus and minus end with different growth rates.

Functional Forms of Actin

• Contractile Bundles: Loosely parallel bundles for cytokinesis, movement of organelles, and vesicles.
• Gel-Like Networks: Structural basis for the cell cortex.
• Bundles: Form the core of microvilli.
• Focal Points/Focal Adhesions: Cell-matrix contact points.