Cytoskeleton: Filaments and Their Functions

• The cytoskeleton provides cell shape, structure, and mechanical stability.
• It enables cell motility and mediates intracellular transport.
• It also supports intracellular organization and reinforces cell-cell connections.

Actin Filaments (Microfilaments)

• Structure: 5-9 nm diameter, flexible, polar, and composed of G-actin subunits.
• Function: Cell motility, shape, and intracellular transport.
• Dynamics: Exhibit preferential growth at the plus end, ATPase activity, and branching.

Microtubules

• Structure: 25 nm diameter, hollow tubes made of α- and β-tubulin dimers, stiff, and polar.
• Function: Intracellular transport and mitotic chromosome separation.
• Dynamics: Plus end growth, GTPase activity, and motor protein interactions with kinesins and dyneins.

Intermediate Filaments

• Structure: Approximately 10 nm diameter, flexible, extensible, and rope-like.
• Function: Structural support and mechanical stability.
• Dynamics: Do not utilize motor proteins, stable, and lack polarity.

Actin Major Functions

• Cell shape and support by forming the cortical skeleton.
• Motility is powered by cellular protrusions and retractions.
• Muscle contraction occurs through interaction with myosin.
• Cytokinesis is achieved via the contractile ring in cell division.
• Intracellular transport facilitates vesicle and organelle movement.

Cortical Actin Cytoskeleton

• Structure: Network of actin filaments beneath the plasma membrane.
• Roles: Provides mechanical stability and links to the plasma membrane through spectrin and ankyrin.
• Defects: Spectrin mutations can cause cardiac pathologies, and ankyrin-related mutations are linked to muscular dystrophy.

Actin Bundles Role

• Support microvilli, increasing surface area in cells like intestinal epithelial cells, aiding in nutrient absorption.

Actin Belts Role

• Form a continuous ring of filaments around epithelial cells, reinforcing adherens junctions and enabling tissue integrity.

Actin-Mediated Processes

• Protrusion: Actin polymerization at the leading edge forms lamellipodia and filopodia.
• Attachment: Focal adhesions anchor the cell to the substratum.
• Traction: Myosin II contraction at the rear generates tension to propel the cell forward.

Actin Filaments

• Parallel bundles: Tight alignment of filaments (e.g., filopodia).
• Antiparallel bundles: Contractile structures (e.g., stress fibers).
• Branched networks: Created by Arp2/3, forming dense meshworks in lamellipodia.

Lamellipodia

• Flat, sheet-like protrusions for cell movement.

Filopodia

• Thin, finger-like projections for exploration and signaling.
• Both structures rely on actin polymerization for extension.

Actin Filaments (F-Actin)

• Form from actin subunits (G-actin).
• ATP hydrolysis promotes filament growth at the plus end.
• Treadmilling: Filament turnover with simultaneous polymerization at the plus end and depolymerization at the minus end.
• Polarity: Actin filaments have distinct plus and minus ends.

Actin-Binding Proteins

• Arp2/3 initiates filament branching.
• Formin promotes the formation of unbranched filaments.
• Tropomyosin stabilizes filaments by binding along their length.

Plasma Membrane Protrusions

• Actin polymerization at the leading edge pushes the membrane forward.
• Actin exerts mechanical force by polymerizing against the membrane, creating protrusions.

Rho Proteins

• GTPases that regulate actin remodeling.
• Activate formin for nucleation and Arp2/3 for branching.

Bacterial Comets

• Pathogens like Listeria monocytogenes hijack actin polymerization, creating "comet tails" that propel the bacteria through the cytoplasm, mimicking eukaryotic motility.

Focal Adhesions

• Actin-linked sites that anchor cells to the extracellular matrix (ECM).

Stress Fibers

• Contractile actin bundles powered by myosin II, providing force for motility.

Myosin II

• Structure: Two-headed motor protein with a globular head (ATP hydrolysis) and a helical tail.
• Function: Enables contraction by sliding actin filaments.

Skeletal Muscle Fibers

• Multinucleate cells with myofibrils composed of sarcomeres.
• Sarcomeres contain actin (thin) and myosin (thick) filaments.

Muscle Contraction

• Calcium binds to troponin, moving tropomyosin and exposing actin sites.
• Troponin regulates contraction by responding to calcium.