cytoskeleton

The Cytoskeleton

  • Definition: A network of protein fibers that provides structural support, extracellular structure, and motility for cells.

  • Dynamic Instability: Most cytoskeletal elements constantly assemble and disassemble to adapt cell structure and function to its needs.

Cytoskeletal Components

1. Intermediate Filaments

  • Size: ~10 nm diameter.

  • Function:

    • Provide mechanical strength to resist stretching forces.

    • Act as scaffolding for anchoring cytoskeletal elements.

    • Minimal role in motility.

  • Structure:

    • Composed of tetramers formed by non-covalent interactions.

    • Tetramers bind end-to-end and side-by-side to form rope-like structures.

    • Associated with plectins, which crosslink filaments and connect them to other cytoskeletal elements.

  • Locations:

    • Found in both cytoplasmic and nuclear regions.

    • Nuclear Lamins:

      • Form the nuclear lamina, a structural network supporting the nuclear envelope.

      • Disassembled during mitosis by MPF phosphorylation.

  • Diseases:

    • Hutchinson-Gilford Progeria Syndrome (HGPS):

      • Caused by mutations in the LMNA gene.

      • Results in defective lamin A, leading to premature aging and impaired nuclear structure.

    • Epidermolysis Bullosa (EB):

      • Inherited disorder causing blistering due to weakened anchoring between the epidermis and dermis.

      • Often caused by mutations in keratin or plectin genes.

2. Microtubules

  • Size: ~25 nm diameter (largest cytoskeletal element).

  • Function:

    • Intracellular transport, organelle positioning, cell motility, mitosis, and structural support.

    • Provide tracks for motor proteins like kinesin and dynein.

  • Structure:

    • Composed of α- and β-tubulin dimers.

    • Polarized structure with a (+) end (faster growth) and a (-) end.

    • Energy-dependent polymerization driven by GTP bound to β-tubulin.

    • Dynamic instability: Tubules polymerize and depolymerize as needed.

  • Key Structures:

    • Microtubule Organizing Centers (MTOCs):

      • E.g., Centrosomes, composed of two centrioles.

      • Serve as nucleation sites for microtubule growth.

    • Cilia and Flagella:

      • Motility structures powered by dynein motor proteins.

      • Cilia move substances across cell surfaces (e.g., respiratory tract).

      • Flagella provide cell motility (e.g., sperm cells).

  • Motor Proteins:

    • Kinesin: Moves cargo toward the (+) end (anterograde transport).

    • Dynein: Moves cargo toward the (-) end (retrograde transport).

  • Drugs:

    • Taxol: Stabilizes microtubules to prevent disassembly; used in cancer therapy.

    • Colchicine: Prevents polymerization; disrupts mitosis.

3. Actin Microfilaments

  • Size: ~7 nm diameter (smallest cytoskeletal element).

  • Function:

    • Provide cell shape and mechanical support.

    • Facilitate membrane changes and motility.

    • Key roles in cytokinesis, chemotaxis, and phagocytosis/pinocytosis.

  • Structure:

    • Comprised of actin monomers.

    • Polymerize at the (+) end using ATP, while depolymerizing at the (-) end (treadmilling).

    • Interact with numerous actin-binding proteins (e.g., myosin).

  • Processes:

    • Microvilli: Increase surface area for absorption.

    • Amoeboid Movement:

      • Formation of pseudopodia (protrusions for movement).

      • Powered by actin rearrangement and myosin contractility.

    • Actin-Myosin Interactions:

      • Myosin motor proteins bind to actin filaments and generate contractile forces.

      • Essential for muscle contraction and intracellular transport.

  • Muscle Contraction:

    • Involves sliding of actin (thin) and myosin (thick) filaments.

    • Troponin (calcium-binding protein) and tropomyosin regulate binding sites for myosin on actin.

    • Requires ATP for cross-bridge cycling and detachment.

    • Rigor Mortis:

      • Post-mortem stiffness caused by lack of ATP to detach actin-myosin cross-bridges.

Summary of Key Differences

FeatureIntermediate FilamentsMicrotubulesActin Microfilaments

Size

~10 nm

~25 nm

~7 nm

Function

Mechanical strength

Transport, motility, mitosis

Shape, motility, membrane changes

Structure

Non-covalent tetramers

Tubulin dimers

Actin monomers

Motor Proteins

None

Kinesin, Dynein

Myosin

Dynamic Instability

Minimal

Highly dynamic

Treadmilling

Key Examples

Nuclear lamina, keratin

Centrosomes, cilia, flagella

Pseudopodia, microvilli

Practice Questions

  1. What are the roles of intermediate filaments in maintaining nuclear structure?

  2. How does dynamic instability differ between microtubules and actin filaments?

  3. Compare and contrast kinesin and dynein motor proteins.

  4. What are the molecular mechanisms driving muscle contraction?

  5. Explain the role of actin in amoeboid movement and pseudopodia formation.

  6. What structural differences allow microtubules and actin filaments to perform distinct cellular functions?