The Cytoskeleton and Molecular Motors: Structure and Function

The Cytoskeleton and Molecular Motors

Overview of the Cytoskeleton

The cytoskeleton is a dynamic network of protein filaments that provides structural support, shape, and organization to eukaryotic cells. It also plays a crucial role in intracellular transport, cell division, and cell movement.

• Cytoskeleton Components: The cytoskeleton consists of three main types of protein filaments:

  • Microfilaments (Actin Filaments): Composed of actin protein; involved in cell shape, movement, and muscle contraction.

  • Microtubules: Hollow tubes made of α- and β-tubulin dimers; provide tracks for organelle movement and are essential for cell division.

  • Intermediate Filaments: Various proteins (e.g., keratin); provide mechanical strength to cells and tissues.

• Functions:

  • Maintaining cell shape

  • Providing mechanical support

  • Facilitating intracellular transport

  • Enabling cell motility and division

Microtubules and Their Motors

Structure and Organization of Microtubules

Microtubules are cylindrical polymers that play a central role in maintaining cell structure and facilitating intracellular transport.

• Composition: Made of α- and β-tubulin dimers arranged in 13 protofilaments to form a hollow tube.

• Polarity: Microtubules have a 'plus end' (favored for assembly/growth) and a 'minus end' (favored for disassembly).

• Microtubule Organizing Center (MTOC): The centrosome acts as the primary MTOC, nucleating microtubule growth and stabilizing minus ends via γ-tubulin complexes.

• Dynamic Instability: Microtubules undergo rapid phases of growth and shrinkage, regulated by GTP hydrolysis on tubulin subunits.

Equation:

$\text{Tubulin-GTP} \rightarrow \text{Tubulin-GDP} + \text{P}_i$

• Taxol: A chemotherapy drug that binds to and stabilizes microtubules, preventing their disassembly and blocking cell division.

Microtubule Motor Proteins

Motor proteins use the energy from ATP hydrolysis to move along microtubules, transporting cellular cargo.

• Kinesin: Moves cargo toward the microtubule plus end (anterograde transport, usually toward the cell periphery).

• Dynein: Moves cargo toward the minus end (retrograde transport, usually toward the cell center).

• Mechanism: Motor proteins have globular heads that bind to microtubules and hydrolyze ATP to generate movement.

ATP Hydrolysis Reaction:

$\text{ATP} \rightarrow \text{ADP} + \text{P}_i$

• Processivity: Kinesin is highly processive, meaning it can take many steps along a microtubule without dissociating, due to coordinated binding of its two heads.

• Affinity Changes: ATP binding increases the motor head's affinity for the microtubule, while ADP binding decreases it.

Example: In nerve cells, kinesin transports vesicles and organelles from the cell body to the axon terminal, while dynein moves materials in the opposite direction.

Microfilaments and Their Motors

Structure and Dynamics of Actin Filaments

Actin filaments (microfilaments) are thin, flexible protein threads that support cell shape and enable movement.

• Composition: Polymers of actin monomers arranged in a double helix.

• Polarity: Have a 'plus end' (fast-growing) and a 'minus end' (slow-growing or shrinking).

• ATP Hydrolysis: Actin monomers bind ATP, which is hydrolyzed to ADP after incorporation into the filament, promoting dynamic assembly and disassembly.

• Regulation: Actin-binding proteins control filament nucleation, growth, and organization.

Equation:

$\text{Actin-ATP} \rightarrow \text{Actin-ADP} + \text{P}_i$

Myosin Motor Proteins

Myosins are a family of actin-dependent motor proteins that convert chemical energy from ATP hydrolysis into mechanical work, such as muscle contraction.

• Structure: Myosin II (muscle myosin) forms bipolar filaments with globular heads and coiled-coil tails.

• Mechanism: Myosin heads bind to actin, hydrolyze ATP, and undergo conformational changes that produce movement (the 'power stroke').

• Cycle:

  1. ATP binding causes myosin to release actin.

  2. ATP hydrolysis 'cocks' the myosin head.

  3. Weak binding to a new actin site triggers phosphate release and the power stroke.

  4. ADP is released, and myosin remains attached until another ATP binds.

• Processivity: Muscle myosin is not processive; each head works independently.

Example: In skeletal muscle, myosin II filaments slide actin filaments past each other, shortening the sarcomere and causing muscle contraction.

Muscle Structure and Contraction

Muscle cells are large, multinucleate cells formed by the fusion of progenitor cells. The basic contractile unit is the sarcomere, composed of overlapping actin (thin) and myosin (thick) filaments.

• Sarcomere: Repeating unit (~2.2 μm) between two Z-discs in muscle fibers.

• Sliding Filament Mechanism: Muscle contraction occurs as myosin heads walk along actin filaments, pulling them toward the center of the sarcomere.

Additional info: The coordinated action of myosin and actin is regulated by calcium ions and associated regulatory proteins (troponin and tropomyosin) in muscle cells.