Microfilaments and Actin Cytoskeleton: Structure, Function, and Regulation

Chapter 13: Cytoskeletal Systems

Introduction to Microfilaments

The cytoskeleton is a dynamic network of protein filaments that provides structural support, facilitates cell movement, and organizes cellular components. Microfilaments, also known as actin filaments, are the smallest of the cytoskeletal filaments and play crucial roles in various cellular processes.

• Definition: Microfilaments are thin, flexible protein filaments composed primarily of actin.

• Key Functions: Involved in cell migration, amoeboid movement, cytoplasmic streaming, and muscle contraction.

• Distribution: Present in all eukaryotic cells, not just muscle cells.

Additional Roles of Microfilaments

Beyond their structural role, microfilaments contribute to cell shape and organization.

• Cell Shape: Microfilaments help maintain and alter cell shape, especially near the plasma membrane.

• Microvilli: Provide structural support to microvilli, increasing surface area for absorption.

Actin: The Building Block of Microfilaments

Actin Monomers and Polymerization

Actin is a highly abundant protein in eukaryotic cells, existing in two forms: monomeric (G-actin) and filamentous (F-actin).

• G-actin: Globular actin monomers that bind ATP or ADP.

• F-actin: Linear polymers of G-actin, forming microfilaments.

• Polymerization: G-actin monomers polymerize into F-actin filaments, a process regulated by nucleotide binding and hydrolysis.

• Equation: $G\text{-actin} \xrightarrow{polymerization} F\text{-actin}$

Note: Tubulin is the same molecule in microtubules, but its function depends on polymerization status.

Types of Actin in Cells

Actin is highly conserved but exists in several isoforms:

• Muscle-specific actins: α-actin

• Nonmuscle actins: β-actin and γ-actin

• Different isoforms localize to specific regions of the cell.

Polarity of Microfilaments

Microfilaments are polar structures with distinct plus (barbed) and minus (pointed) ends.

• Plus end: Rapid addition of actin monomers.

• Minus end: Slower addition or loss of monomers.

• Polarity is essential for directional movement and cellular processes.

Regulation of Actin Polymerization

Actin-Binding Proteins

Cells use a variety of actin-binding proteins to regulate the assembly, length, and organization of actin filaments.

• ADF/cofilin: Binds ADP-actin and increases turnover of ADP-actin at the minus end of microfilaments.

• Profilin: Competes with thymosin β4 for G-actin binding, promoting polymerization.

• Thymosin β4: Sequesters G-actin, preventing polymerization.

• Capping proteins: Bind to filament ends to prevent further loss or addition of subunits.

• Severing proteins: Gelsolin breaks actin filaments and caps the newly exposed ends.

• Crosslinking proteins: Filamin forms networks by joining two microfilaments at angles.

Microfilament-Targeting Drugs

Certain drugs and toxins can disrupt or stabilize microfilaments:

• Cytochalasins: Fungal metabolites that prevent addition of new actin monomers.

• Latrunculin A: Sequesters actin monomers, preventing their addition to filaments.

• Phalloidin: Stabilizes microfilaments and prevents depolymerization; derived from death cap mushrooms.

Organization of Actin Structures in Cells

Higher-Order Actin Assemblies

Actin filaments can be organized into bundles, networks, and specialized structures:

• Stress fibers: Bundles of actin in cells adhering tightly to substrates.

• Cell cortex: Network of actin filaments beneath the plasma membrane.

• Lamellipodia: Broad, sheet-like protrusions at the leading edge of migrating cells.

• Filopodia: Thin, spike-like projections containing tightly bundled actin filaments.

Microvilli

Microvilli are finger-like projections on the cell surface, especially prominent in intestinal epithelial cells.

• Structure: Core of microvilli consists of tightly bundled actin filaments with plus ends at the tip.

• Function: Increase surface area for absorption.

Crosslinks and the Terminal Web

Microfilaments are connected to the plasma membrane and to each other via crosslinking proteins.

• Crosslinking proteins: Myosin I, calmodulin, fimbrin, and villin.

• Terminal web: Network of filaments at the base of microvilli, composed mainly of spectrin and myosin II.

• Provides structural support and links microfilaments to the membrane and intermediate filaments.

Actin in Cell Motility

Role in Cell Movement

Actin polymerization drives cell motility, especially in structures like lamellipodia and filopodia.

• New actin filaments are added at the leading edge, pushing the plasma membrane forward.

• Drugs that inhibit actin polymerization block cell movement.

• Coordinated assembly and disassembly of actin filaments at the front and rear of the cell enable migration.

Summary Table: Key Actin-Binding Proteins and Their Functions

Protein	Function	Additional info
ADF/cofilin	Binds ADP-actin, increases turnover at minus end	Promotes filament disassembly
Profilin	Promotes actin polymerization	Competes with thymosin β4
Thymosin β4	Sequesters G-actin, inhibits polymerization	Regulates actin monomer pool
Gelsolin	Severs filaments, caps ends	Prevents further polymerization
Filamin	Crosslinks filaments into networks	Important in cell cortex
Fimbrin/Villin	Bundles actin filaments	Found in microvilli

Conclusion

Microfilaments, composed of actin, are essential for maintaining cell shape, enabling movement, and organizing cellular structures. Their dynamic assembly and regulation by various proteins and external agents underscore their importance in cell biology.