The Cytoskeleton: Structure, Components, and Functions in Eukaryotic Cells

Cytoskeleton Overview

Definition and Functions

The cytoskeleton is a dynamic network of protein filaments found in the cytoplasm of eukaryotic cells. It provides structural support, determines cell shape, enables cellular movement, and facilitates intracellular transport. The cytoskeleton is essential for cell division, contraction, and anchoring cells to their environment.

• Cell shape and support: Maintains cell integrity and morphology.

• Intracellular framework: Organizes organelles and cytoplasmic components.

• Intracellular movement: Transports vesicles and organelles.

• Cellular movement: Enables motility via specialized structures.

• Cellular contraction: Drives muscle contraction and cytokinesis.

• Response to signals: Modifies structure in response to extracellular cues.

• Endocytosis/exocytosis: Facilitates vesicle formation and fusion.

• Cell division: Segregates chromosomes and splits cells.

• Anchorage: Links cells to the extracellular matrix and other cells.

Main Components of the Cytoskeleton

Comparison Table

VComponent	Polymer	Subunit	Diameter	Structure	Polarity	Main Functions
Microtubules (MT)	Protofilaments (13)	α/β-tubulin heterodimers	25 nm	Hollow tube	Yes	Cell shape, organelle movement, mitosis, cilia/flagella structure
Microfilaments (MF)	F-actin	G-actin monomers	7 nm	Two-stranded helix	Yes	Cell movement, muscle contraction, cell division, shape
Intermediate Filaments (IF)	Fibrous proteins	Various (keratin, vimentin, etc.)	8–12 nm	Rope-like fibers	No	Mechanical strength, cell shape, nuclear envelope support

General Characteristics of Cytoskeletal Elements

• Abundance: Easily visualized by fluorescence microscopy.

• Modularity: Built from a few basic subunits (e.g., α/β-tubulin, actin).

• Dynamic nature: Capable of rapid assembly/disassembly (polymerization/depolymerization).

• Associated proteins: Cytoskeleton-associated proteins regulate assembly, stability, and function.

Microtubules (MT)

Structure and Assembly

• Composition: Hollow tubes of 13 protofilaments made from α/β-tubulin heterodimers.

• Polarity: Plus (+) and minus (−) ends; growth occurs mainly at the plus end.

• Types: Singlet (cytoplasmic), doublet/triplet (axonemal, centriolar).

Tubulin Subunits

• α-tubulin and β-tubulin: Form heterodimers; both bind GTP for polymerization.

• Polymerization: Tubulin dimers assemble into protofilaments, forming the microtubule.

Microtubule Formation

• Growth at the plus end is regulated by a GTP cap; minus end is stabilized by γ-tubulin.

• Lack of GTP-tubulin leads to microtubule catastrophe (rapid depolymerization).

Microtubule-Associated Proteins: Kinesin and Dynein

• Kinesin: Motor protein moving cargo toward the plus end (anterograde transport).

• Dynein: Motor protein moving cargo toward the minus end (retrograde transport).

• Both use ATP for movement and have globular heads that bind MTs.

Functions of Microtubules

• Serve as tracks for organelle and vesicle movement (e.g., Golgi, ER, plasma membrane).

• Form the structural basis of cilia and flagella (axonemal MTs).

• Participate in mitosis by forming the mitotic spindle and segregating chromosomes.

Cilia and Flagella

• Structure: Axoneme (9+2 arrangement of MTs), covered by plasma membrane.

• Basal body: 9x3 structure, nucleation point for MT assembly.

• Cilia: Short, numerous, beat in coordinated patterns for movement or sensory functions.

• Flagella: Longer, fewer per cell, enable motility (e.g., sperm cell).

Clinical Relevance: Ciliopathies and Cancer Therapy

• Ciliopathies: Genetic disorders affecting cilia function, leading to developmental, homeostatic, and reproductive issues.

• Situs inversus: Reversal of organ position, often linked to dynein mutations (Kartagener syndrome).

• Microtubule inhibitors: Drugs (taxanes, vinca alkaloids) disrupt MT function, block mitosis, and are used in cancer therapy.

Drug Class	Source	Mechanism	Examples
Taxanes	Genus Taxus (yew)	Stabilize microtubules, prevent depolymerization	Docetaxel, paclitaxel
Vinca alkaloids	Catharanthus roseus (periwinkle)	Inhibit microtubule polymerization	Vincristine, vinblastine

Microfilaments (MF)

Structure and Assembly

• Composition: Polymers of actin (G-actin monomers assemble into F-actin).

• Polarity: Plus (+) and minus (−) ends; growth occurs at the plus end.

• Diameter: 7 nm.

Actin Polymerization

• G-actin binds ATP, which is necessary for polymerization.

• ATP hydrolysis to ADP occurs after incorporation into the filament.

Actin-Binding Proteins

• Regulate filament growth, decay, and anchoring.

• Types: monomer-binding, severing, bundling, crosslinking, capping, anchoring proteins.

Myosins

• Superfamily of motor proteins interacting with actin filaments.

• Structure: head (binds actin, uses ATP), neck (flexible, regulatory), tail (binds cargo).

Functions of Microfilaments

• Cell movement (e.g., amoeboid migration, muscle contraction).

• Formation of cellular structures: microvilli, lamellipodia, filopodia, stress fibers.

• Phagocytosis: formation of endocytic vesicles.

• Cell division: contractile ring during cytokinesis.

Specialized Structures

• Microvilli: Non-motile, finger-like projections in intestinal cells, supported by parallel bundles of MF.

• Lamellipodia: Flat, branched MF network at the leading edge of moving cells.

• Filopodia: Thin, long, parallel MF bundles for sensing and movement.

• Stress fibers: Stable bundles of F-actin, myosin II, and a-actinin, anchor cells via focal adhesions.

Cell Migration and Regulation

• MFs drive cell migration in development, immune response, and cancer.

• Regulated by signalling proteins (Rho, Rac, CDC42) that respond to extracellular stimuli.

MFs in Muscle and Cell Division

• Muscle contraction: ATP-dependent sliding of actin and myosin filaments.

• Cell division: Actin contractile ring splits the cell during cytokinesis.

Genetic Diseases of Microfilaments

Protein	Associated Diseases
Actin	Hypertrophic cardiomyopathy, DFNA20, Nemaline myopathy
Myosin	Freeman-Sheldon syndrome, Myopathy, Hearing loss
Tropomyosin/Troponin	Hypertrophic cardiomyopathy, Nemaline myopathy
Titin	Hypertrophic cardiomyopathy

Intermediate Filaments (IF)

Structure and Assembly

• Size: 8–12 nm, intermediate between MT and MF.

• Composition: Various fibrous proteins (keratin, vimentin, desmin, neurofilaments, lamins).

• Structure: Rope-like fibers, assembled from dimers into tetramers, then into protofilaments.

• No polarity: Unlike MT and MF.

• Stability: Most stable and least soluble cytoskeletal component.

Classes of IF

Class	Protein	Cell Type	Function
I, II	Keratin	Epithelial cells	Mechanical strength
III	Vimentin, Desmin	Mesenchymal, muscle cells	Cell shape, sarcomere linkage
IV	Neurofilaments	Neurons	Axon support
V	Lamin	Nucleus	Nuclear envelope support

Functions of Intermediate Filaments

• Provide mechanical strength and resistance to stress.

• Support nuclear envelope (nuclear lamina).

• Cell-type specific functions (e.g., keratin in skin, desmin in muscle).

• Diagnostic markers in cancer pathology.

Genetic Diseases Related to IF

• Keratin mutations: Skin fragility, blistering diseases.

• Desmin mutations: Myopathies affecting muscle and heart.

• Lamin mutations: Progeria (premature aging), nuclear envelope defects.

Cellular Junctions and Cytoskeleton

Role in Cell Adhesion

• MF and IF are involved in cellular junctions (adherens, desmosomes).

• Provide mechanical support and link cells together in tissues.

Summary

• The cytoskeleton is composed of microtubules, microfilaments, and intermediate filaments.

• Each system has distinct structure, assembly, and functions.

• Cytoskeletal proteins and associated diseases have major clinical importance.

Further Reading

• Hardin, Bertoni, Kleinsmith (2013). Becker's World of the Cell, 8th edn. Chapters 13 & 14: The Cytoskeletal Systems and Cellular Movement.