Recording-2025-03-06T16:50:19.838Z

Overview of the Cytoskeleton

• The cytoskeleton is a dynamic structure crucial for cellular functions.

Actin Filaments

• Actin Structure: Composed of globular protein subunits called G-actin.

  • Each actin monomer has a plus end and a minus end, essential for filament assembly.

• Polarity and Dynamics:

  • The plus end grows faster than the minus end.

  • Actin monomers can bind ATP (high affinity) or ADP (low affinity), influencing assembly and disassembly.

  • After monomer incorporation, ATP is hydrolyzed to ADP, impacting stability and dissociation rates.

• Treadmilling:

  • A unique dynamic behavior where the filament appears to maintain a constant length while monomers are added at the plus end and lost from the minus end.

• Actin-Binding Proteins:

  • Hundreds of proteins modulate the dynamics of actin, with various roles including capping, severing, and stabilizing filaments.

  • Example: Cofilin binds ADP-bound actin, twisting the filament and promoting disassembly.

Myosin Motor Proteins

• Myosin Structure:

  • Typically exists as dimers with a heavy chain (motor domain) and a long tail region.

  • Plays a key role in muscle contraction and cellular movement.

• Mechanism of Action:

  1. ATP Binding: Myosin head is tightly bound to actin filament and releases upon ATP binding.

  2. Hydrolysis: ATP is hydrolyzed, causing conformational changes in myosin to the 'cocked' position (high energy state).

  3. Binding to Actin: Myosin rebinds to actin at a new position.

  4. Power Stroke: Release of the inorganic phosphate triggers a conformational shift that moves myosin, causing contraction.

  5. Release of ADP: The cycle resets when ATP binds to myosin again.

• Role in Muscle Contraction:

  • Myosin pulls actin filaments together, leading to contraction of muscle fibers through coordinated activity regulated by calcium ions.

Microtubules

• Structure: Made up of tubulin dimers (alpha and beta) assembled into protofilaments that form a hollow tube.

  • Microtubules consist of 13 protofilaments arranged in a ring.

• Dynamics: Similar to actin but with key differences in GTP binding/hydrolysis leading to "catastrophe,” a rapid disassembly process when GTP caps are lost.

• Dynamic Instability: Microtubules continuously grow and shrink, allowing rapid rearrangements necessary for cell functions (e.g., intracellular transport).

Nucleation of Microtubules

• Nucleation typically requires external proteins like gamma-tubulin, forming gamma-tubulin ring complexes that serve as templates for new microtubule formation.

• Microtubule Organizing Centers (MTOCs): Microtubules emanate from these centers, typically the centrosome, which is crucial for organizing microtubules and coordinating cellular functions.