Cytoskeletal Microtubules and Motility

Cytoskeletal Microtubules & Microfilaments & Motility

• Students will be able to correlate the molecular organization of microtubules with their dynamic nature.
• Students will be able to analyze the structural adaptations of microtubules to their function.
• Students will be able to correlate the motor proteins involved in cell trafficking with microtubules.
• Students will understand the importance of microtubules as a drug target.
• Students will be able to correlate the molecular structure of actin with its function.

Cytoskeleton

• The cytoplasm of animal cells contains a cytoskeleton, a complex 3D network of protein filaments.
• This network maintains cell shape and enables cellular movement of organelles and vesicles.
• The cytoskeleton comprises three components: microfilaments, intermediate filaments, and microtubules.

Microtubules

• Microtubules (MTs) are hollow structures, acting as intracellular pathways.
• The centrosome, near the nucleus, contains centrioles and ring-shaped tubulin complexes for MT nucleation.
• MTs are dynamic, growing and shrinking at their plus ends (away from the nucleus). The average half-life is about 10 minutes.
• MTs are composed of 13 parallel protofilaments of globular tubulin heterodimers.

Functions of Microtubules

• Provide cell shape and rigidity.
• Regulate the intracellular movements of organelles and vesicles.
• Establish intracellular compartments.
• Enable ciliary and flagellar (sperm tail) movement.
• Important in cell division, forming the mitotic spindle.

Clinical Correlation

• Drugs like colchicine disrupt MT formation, affecting leukocyte function and inflammatory responses (e.g., gout).

Microtubule-Associated Proteins (MAPs)

• Motor proteins assist in the transport of organelles and vesicles within the cell.

Centrioles

• Cylindrical structures composed of nine microtubule triplets, forming the core of the centrosome.
• Crucial for microtubule formation and organization. Involved in cell division, guiding the formation of cilia and flagella.

Actin Filaments (Microfilaments)

• Composed of two intertwined chains of globular actin (G-actin) subunits forming a filamentous structure (F-actin).
• Typically 6nm thick.
• Feature a faster-growing plus end and a slower-growing minus end.

Functional Forms of Actin

• Contractile bundles: Loosely arranged parallel filaments, crucial for cytokinesis (cleavage furrow formation).
• Gel-like networks: Provide structural support to the cell cortex.
• Bundles: Form the core of microvilli.
• Focal points: Points of contact with the extracellular matrix.

Cell Cycle Control & Mitosis

• Cyclin proteins and cyclin-dependent kinases (CDKs) control the cell cycle.
• Different cyclin/CDK complexes drive transitions between phases.
• Checkpoints ensure accurate DNA replication and chromosome segregation during mitosis.
• Mutations disrupting cell cycle control can lead to uncontrolled cell proliferation (cancer).

Chromosomes

• Chromosomes condense during mitosis and meiosis, becoming visible under a light microscope.
• Each chromosome consists of two sister chromatids joined at a centromere.
• Chromosomes carry the duplicated DNA.

Types of Cells in the Human body

• Somatic cells: Body cells with 46 chromosomes (23 homologous pairs).
• Germ cells: Reproductive cells with 23 chromosomes. (Haploid).

Mitosis

• Division of somatic cells to produce two identical daughter cells.
• Consists of four phases: prophase, metaphase, anaphase, and telophase.