Cytoskeleton and Cell Motility: Actin Filaments

Actin Filaments and Cell Motility

• Overview of Actin Filaments

  • Actin filaments play a vital role in cellular movement and structural integrity.
  • High levels of actin monomers are present in animal cells, sufficient for spontaneous polymerization in vitro.

• Role of Actin Binding Proteins

  • Actin binding proteins modulate the dynamics of actin filaments:
  • Sequestering Proteins: Keep actin monomers available for polymerization by preventing them from forming filaments.
  • Bundling Proteins: Form parallel structures that are essential for structures like microvilli.
  • Motor Proteins (e.g., Myosin): Facilitate movement; involved in muscle contraction and organelle movement in plants.
  • Capping Proteins: Stabilize actin filaments by preventing depolymerization.
  • Cross-linking Proteins: Form a gel-like network (cell cortex) that supports the plasma membrane.
  • Severing Proteins: Break down actin filaments, influencing filament dynamics and cellular flexibility.

• Function of the Cell Cortex

  • Composed of actin filaments providing mechanical support and shape to the plasma membrane.
  • Plays a key role in cellular locomotion: allows cells to change shape and send projections into the environment (e.g., amoeboid movement, neuronal growth).

• Steps of Cell Movement

  1. Protrusion Formation:
  • Driven by actin polymerization, resulting in the formation of lamellipodia (broad, flat projections) and filopodia (thin, stiff projections).
  • Growth direction is towards the plus end of actin filaments, oriented towards the membrane.
  1. Surface Attachment:
  • Protrusions anchor to surfaces through integrin binding, involving connections between intracellular actin filaments and extracellular components.
  1. Cell Body Movement:
  • Uses myosin motor proteins to contract and pull the rear of the cell forward.

• Motor Protein Functionality

  • Myosin Motor Proteins:
  • Myosins generate movement along actin filaments utilizing ATP hydrolysis.
  • Two classes:
    • Myosin I: Found in various cell types.
    • Myosin II: Primarily in muscle cells; dimeric structure with two heads.
  • Movement occurs via head binding, detachment, and re-binding to actin filaments in a sequence of steps leading to contraction.

• Cytokinesis and Cell Division

  • Actin and myosin form a contractile ring during cytokinesis, constricting the cell to form two daughter cells.
  • Orientation of the contractile ring is guided by interpolar microtubules.

• Rho GTPase Signaling

  • Monomeric G proteins (e.g., Rho, Rac, CDC42) influence actin dynamics and responses to extracellular signals.
  • Activation leads to specific actin structures:
  • Rho promotes bundling, Rac induces lamellipodia, CDC42 fosters filopodia.

• Muscle Contraction Mechanism

  • Muscle cells utilize myosin II in a structured manner within myofibrils (functional units called sarcomeres).
  • Contraction occurs through the sliding filament mechanism where myosin heads move along actin filaments, shortening the sarcomere in multiple steps:
  1. Attached State: Myosin bound to actin.
  2. Released State: Myosin head binds ATP, causing detachment.
  3. Cocked State: ATP hydrolyzed, moving myosin head along the filament.
  4. Force-Generating State: Phosphate release tightens binding and moves filament.

• Regulation of Contraction

  • Calcium ions act as signals, triggering conformational changes in proteins like troponin and tropomyosin regulating actin-myosin interactions.
  • Contraction stops upon calcium removal via pumps, reverting regulatory proteins to block myosin binding.

• Conclusion

  • The integration of actin dynamics with extracellular signaling allows precise cellular responses to environmental changes and is crucial for muscle contraction and cell motility.