Cytoskeleton: Actin and Microtubules Overview

Key Concepts in Cytoskeleton

Types + Function of the Cytoskeleton

  • Actin Filaments

    • Microvilli: Projections that increase surface area and are primarily made of actin.

    • Functionality:

      • Force generation for cellular movement.

      • Controlling cell shape.

      • Cellular adhesion, influencing how cells stick together.

    • Different types of Actin Filaments:

      • single

      • microvilli

      • stress fibers

      • striated muscles

  • Globular + Filamentous Actin

    • G-actin are ATPases that bind + hydrolyze H2O

      • are also asymmetrical (has plus and minus ends

    • F-actin are made up of 2 G-actin strands

  • Tubules

    • GTPases (can exist in GTP or GDP bound states)

  • Microtubules

    • made up of alpha-tubulin + beta-tubulin (tubulin dimers)

      • creates a polarized filament where 13 of them can form a microtubule

    • Functions:

      • cell division

      • exocytosis

      • cell/organelle movement

Processes of the Cytoskeleton

  • Processes:

    • Dynamic Process

      • fast-changing process

      • e.g., cell division, where actin forms the contractile ring to split the cell during cytokinesis and microtubules form the mitotic spindle to separate the chromosomes during mitosis

    • Stable Process

      • extremely slow changes

      • e.g., in epithelial tissues:

        • actin forms microvilli

        • microtubules forms transport tracks

        • intermediate filaments stabilizes desmosomes (cell connections)

  • Regulation of the Cytoskeleton:

    • Assembly + Disassembly

      • g-actin subunits are held together by non-cova bonds to create f-actin polymers

      • for protofilaments, the more polymers are tgt = stronger + more stable

        • less polymers = energy is more evenly spread out = easier to break bonds

    • Nucleation (Lag Phase)

      • nucleation: process of forming new cytoskeleton (beginning the cytoskeleton is rate limiting)

      • 3 phases: lag phase, elongation phase, steady state

Cytoskeleton Kinetics

  • Treadmilling:

    • A dynamic process in which actin filaments grow at one end (plus end) while shrinking at the other end (minus end).

    • Occurs at a critical concentration of actin monomers.

    • Treadmilling is influenced by ATP hydrolysis (the conversion of ATP to ADP), which stabilizes the polymer.

    • Cc(T) < C < Cc(D)

  • Rates

    • polymerization = add polymers

      • rate constant: Kon

      • rate: Rpol = kdepolarization C Kon

        • C = [free monomer]

    • depolymerization = remove polymers

      • rate constant = koff

      • rate: Rdepol = koff

  • Critical Concentration (Cc):

    • when rate of polymerization = rate of depolymerization

      • results in no net change in filament length (equilibrium)

  • Polymerization

    • + end = more dynamic —> can (de)polymerize faster than - end

    • monomers + polymers

      • G-actin = monomer —> can change shape to attach to - end of polymer

      • G-actin monomer can be added to +/- end

        • + end is added more quickly bc the shape is more favourable

        • - end is added more slowly bc the shape is less favourable

    • nucleotide binding

      • NTP-subunits > NDP-subunits (better affinity)

        • ADP actin has low affinitiy

        • ATP actin has high affinity and will change shape + become D when connected

      • T-subunit looks like G-actin subunit (before conformation change) —> tubulin GTP, actin ATP

      • T-subunit polymerizes into D-subunit —> actin ADP, tubulin GTP

      • at equilibrium, Cc(T) < Cc(D)