Cytoskeleton and Its Components

Cytoskeleton Overview

  • The cytoskeleton is a dynamic and complex network of protein filaments within the cytoplasm that:
    • Provides structural support
    • Maintains cell shape
    • Enables intracellular transport
    • Facilitates cellular movement and division
    • Enhances mechanical resilience

Types of Protein Filaments

  1. Intermediate Filaments

    • Composed of fibrous proteins; about 10 nm in diameter
    • Provide mechanical strength to cells, enabling them to withstand mechanical stress
    • Most stable and durable components of the cytoskeleton
    • Found throughout the cytoplasm, particularly around the nucleus and at cell junctions like desmosomes
    • Examples include keratin (in epithelial cells), vimentin (in connective tissue and muscle), neurofilaments (in nerve cells), and nuclear lamins (support nuclear envelope)
      • Keratin Filaments: Offer resilience to stress, found in skin, hair, nails.
      • Linked to diseases like epidermolysis bullosa simplex due to mutations in keratin genes.
      • Vimentin: Present in connective tissues and muscle cells.
      • Neurofilaments: Support axonal structure in neurons.
      • Nuclear Lamins: Provide structural support to the nucleus, aiding chromatin organization and nuclear envelope assembly.

  2. Microtubules

    • Composed of tubulin (α-tubulin and β-tubulin); about 25 nm in diameter
    • Hollow, cylindrical, and dynamic structures
    • Functions include:
      • Maintaining cell shape and resisting compression
      • Serving as tracks for intracellular transport via motor proteins (kinesins and dyneins)
      • Forming the mitotic spindle for chromosome segregation during cell division
    • Dynamic instability allows rapid assembly and disassembly
    • Originate from Microtubule-Organizing Centers (MTOCs) such as the centrosome.

  3. Actin Filaments (Microfilaments)

    • Composed of actin subunits; about 7 nm in diameter
    • Involved in cell shape, motility, and intracellular transport
    • Essential for processes like cytokinesis and cellular contraction
    • Actin filaments have plus and minus ends, with growth occurring preferentially at the plus end.

Centrosome - Major Microtubule-Organizing Center

  • Located near the nucleus in animal cells
  • Composed of two centrioles surrounded by pericentriolar material, which contains γ-tubulin ring complexes.
  • Functions include:
    • Nucleation of microtubule growth
    • Establishing spatial organization of microtubules
    • Initiating formation of the mitotic spindle during cell division.

Progeria: A Case Study of Nuclear Lamin Defects

  • A rare genetic disorder (premature aging) caused by mutations in the LMNA gene, leading to defective lamin A production (progerin).
  • Symptoms include:
    • Growth delays
    • Aged appearance, hair loss, cardiovascular issues
    • Nuclear instability and cellular dysfunction due to compromised nuclear envelope.

Accessory Proteins in Intermediate Filaments

  • Proteins like plectin link intermediate filaments to each other and to other cytoskeletal elements (microtubules and actin).
  • Mutations in plectin lead to diseases combining features of epidermolysis bullosa simplex, muscular dystrophy, and neurodegeneration.

Dynamic Instability of Microtubules

  • Refers to the rapid switching between growth and shrinkage, driven by GTP hydrolysis.
  • This allows cells to reorganize their cytoskeleton, probe for targets during mitosis, and facilitate intracellular transport.