Cytoskeleton II: Actin--motility & contractility; Intermediate filaments (2/28)

Protein-Protein Interactions

• Protein-protein interactions are highly specific, with variations in monomers leading to different functional interactions.

• Actin filaments are not formed from single protofilaments but from at least two protofilaments that grow simultaneously.

Structure of Actin Filaments

• Each actin filament is composed of monomers that have polarity:

  • Plus End (fast-growing end)

  • Minus End (slow-growing end)

• Polarity is determined by the shape of the monomers; it does not relate to charge.

Actin vs. Microtubule Formation

• Actin filaments require simpler structures to initiate growth compared to microtubules:

  • Microtubules consist of 13 protofilaments and require precise alignment of tubulin dimers.

  • Actin filaments can grow from two simple protofilaments without a specialized organizing center.

• Regulation of actin filament growth is usually facilitated by actin-binding proteins, allowing for dynamic response to cellular signals.

Hydrolysis and Confirmation Changes

• Actin monomers bind ATP which is subsequently hydrolyzed to ADP:

  • ATP-bound actin has a tighter binding confirmation than ADP-bound actin.

  • The hydrolysis of ATP to ADP leads to confirmation changes in actin, promoting treadmilling behavior.

• The rate of addition at the plus end and loss at the minus end allows actin to appear static while dynamically reshaping cellular structures.

Actin's Role in Cell Motility

• Actin filaments are crucial for cellular activities such as phagocytosis, where actin polymerizes to extend the membrane around particles.

• During cell division, actin forms a contractile ring facilitating the separation of daughter cells.

• Myosins are the motor proteins that interact specifically with actin, utilizing ATP hydrolysis to induce movement along actin filaments.

Myosin-Powered Movement

• Myosins vary in type but generally facilitate movement through interaction with actin filaments:

  • Myosins use ATP hydrolysis to change their shape and walk along actin filaments, analogous to kinesins on microtubules.

  • Myosins can exert force on actin, enabling muscular contractions and various cell movements.

Actin in the Cell Cortex

• The cell cortex is a dense layer of proteins located just beneath the plasma membrane, providing structural support:

  • Actin filaments contribute to maintaining the shape of the cell and interact with membrane proteins.

• The network of actin filaments supports physiological functions in the cell, including maintaining cell integrity.

Actin-Mediated Morphogenesis

• Actin and myosin contribute to cell shape changes necessary for developmental processes:

  • Cells can change shape in processes such as rolling and tube formation during embryogenesis, driven by actin/myosin dynamics.

Intermediate Filaments

• Intermediate filaments, such as keratins, provide structural integrity to tissues, notably in epithelial cells:

  • These filaments form robust networks that endure physical stress.

  • Mutations affecting keratin assembly can lead to significant vulnerabilities, such as blister formation under minor stress.

Conclusion

• The dynamics of actin and myosin within cells enable a variety of cellular functions, from maintaining structure to enabling movement and division.