Cytoskeletal Systems: Structure and Function in Eukaryotic Cells

Chapter 13: Cytoskeletal Systems

Introduction to the Cytoskeleton

The cytoskeleton is a dynamic network of protein filaments and tubules that extends throughout the cytosol of eukaryotic cells. It is essential for maintaining cell shape, enabling cell movement, facilitating intracellular transport, and organizing cellular components. Cytoskeletal elements are also found in some bacteria and archaea.

• Key Functions: Cell movement, cell signaling, organelle movement, cell division, and maintenance of cell shape.

• Major Elements: Microtubules, microfilaments (actin filaments), and intermediate filaments.

Major Structural Elements of the Cytoskeleton

Types of Cytoskeletal Elements

The cytoskeleton consists of three main types of protein filaments:

• Microtubules (MTs): Largest filaments, hollow tubes made of tubulin dimers.

• Microfilaments (MFs): Smallest filaments, composed of actin monomers.

• Intermediate Filaments (IFs): Intermediate size, made of various fibrous proteins.

Microtubules

Structure and Properties

Microtubules are hollow cylinders composed of 13 protofilaments, each made of alternating α-tubulin and β-tubulin heterodimers. They exhibit polarity, with a plus (+) end and a minus (−) end, which affects their growth dynamics.

• Functions: Form mitotic spindles, provide tracks for vesicle transport, shape the cell, and are structural components of cilia and flagella.

• Polarity: Plus end grows faster than the minus end.

• Isoforms: Multiple genes encode slightly different tubulin proteins (tubulin isoforms).

Microtubule Assembly and Dynamics

Microtubule assembly involves nucleation (lag phase), elongation, and steady-state equilibrium. The critical concentration is the tubulin concentration at which assembly and disassembly are balanced.

• Assembly: Tubulin dimers add to the ends of microtubules, primarily at the plus end.

• Treadmilling: Simultaneous addition at the plus end and loss at the minus end.

• Dynamic Instability: Microtubules switch between growth and shrinkage phases, regulated by the presence of a GTP cap at the plus end.

Equation:

$\text{Critical Concentration} = \frac{k_{off}}{k_{on}}$

Regulation by Drugs and Proteins

• Antimitotic Drugs: Colchicine, vinblastine, and vincristine inhibit microtubule assembly; Taxol stabilizes microtubules.

• Microtubule-Associated Proteins (MAPs): Stabilize, bundle, or destabilize microtubules (e.g., Tau, MAP2, +TIPs, catastrophins).

Microtubule-Organizing Centers (MTOCs)

Microtubules originate from MTOCs, such as the centrosome, which contains centrioles and pericentriolar material. γ-tubulin ring complexes (γ-TuRCs) nucleate microtubule assembly.

• Centrosome: Main MTOC in animal cells, organizes spindle during cell division.

• γ-Tubulin: Essential for nucleating new microtubules.

Microfilaments (Actin Filaments)

Structure and Properties

Microfilaments are composed of actin monomers (G-actin) that polymerize to form filamentous actin (F-actin). They are involved in muscle contraction, cell migration, and maintenance of cell shape.

• Polarity: Plus (barbed) end and minus (pointed) end; growth occurs mainly at the plus end.

• Isoforms: α-actin (muscle), β- and γ-actin (non-muscle).

Assembly and Regulation

• Assembly: Nucleation (lag phase), elongation, and steady-state.

• Regulation: Actin-binding proteins control nucleation, severing, capping, bundling, and branching (e.g., Arp2/3 complex, formins).

• Drugs: Cytochalasin D inhibits polymerization; phalloidin stabilizes filaments.

Specialized Structures

• Cell Cortex: Network of microfilaments beneath the plasma membrane.

• Microvilli: Finger-like projections in intestinal cells, increase surface area; core bundle of actin filaments crosslinked by fimbrin and villin.

• Lamellipodia and Filopodia: Protrusions at the leading edge of migrating cells, formed by branched and bundled actin networks.

Intermediate Filaments

Structure and Properties

Intermediate filaments (IFs) are rope-like fibers that provide mechanical strength to cells. They are more stable and less soluble than microtubules and microfilaments.

• Composition: Fibrous proteins, not globular; central rod domain flanked by N- and C-terminal domains.

• Assembly: Dimers form tetramers, which assemble into protofilaments and then into mature filaments.

Classes of Intermediate Filament Proteins

Class	Protein Type	Location
I & II	Keratins	Epithelial cells
III	Vimentin, Desmin, GFAP	Connective tissue, muscle, glial cells
IV	Neurofilament proteins	Nerve cells
V	Lamins (A, B, C)	Nuclear envelope
VI	Nestin	Neural stem cells

Functions

• Mechanical Strength: Resist tension and compression, maintain cell integrity.

• Cellular Organization: Anchor organelles, connect to other cytoskeletal elements via linker proteins (e.g., plectin).

Integration of Cytoskeletal Elements

Coordination and Linker Proteins

The cytoskeleton is a mechanically integrated structure. Linker proteins such as plectin connect intermediate filaments, microtubules, and microfilaments, facilitating coordinated cellular responses and structural integrity.

• Examples: Spectrin-ankyrin-actin network in red blood cells; plectin at sites where intermediate filaments connect to microtubules and microfilaments.

Summary Table: Comparison of Cytoskeletal Elements

Element	Subunit	Structure	Main Functions
Microtubules	α/β-tubulin dimers	Hollow tubes	Cell shape, transport, division
Microfilaments	Actin monomers	Two-stranded helix	Movement, shape, contraction
Intermediate Filaments	Various fibrous proteins	Rope-like fibers	Mechanical strength

Key Terms

• Cytoskeleton: Network of protein filaments in the cell.

• Microtubule: Hollow tube made of tubulin, involved in transport and division.

• Microfilament: Actin filament, involved in movement and shape.

• Intermediate Filament: Fibrous protein filament, provides strength.

• MTOC: Microtubule-organizing center.

• MAPs: Microtubule-associated proteins.

• GTP Cap: Stabilizes growing microtubule ends.

• Dynamic Instability: Rapid switching between growth and shrinkage of microtubules.

• Arp2/3 Complex: Nucleates branched actin networks.

• Plectin: Linker protein connecting cytoskeletal elements.

Example: In neurons, microtubules provide tracks for vesicle transport, actin filaments enable growth cone movement, and neurofilaments maintain axonal integrity.

Additional info: Some details on protein families, drug mechanisms, and specialized structures were expanded for clarity and completeness.