The Cytoskeleton

Identify Major Components: Describe the three major components of the cytoskeleton: microtubules, actin microfilaments, and intermediate filaments; understand their structure, assembly, and cellular functions.
Intermediate Filaments: Identify three cell-type specific types of cytoplasmic intermediate filaments and the function of nuclear lamins.
Filament Orientation: Understand the terminology of plus and minus ends of filaments, specifically microtubules and their relation to cellular structure.
Cytoskeletal Motors: Describe the functions of cytoskeletal motors such as dynein, kinesin, and myosin.
Cell Structures: Identify and recognize structures such as lamellipodium, stress fibers, microvilli, cilia, flagella, and contractile rings in micrographs.
Clinical Correlations: Explain implications of ciliopathies, as well as the effects of taxol and colchicine on intermediate filament types.

Dynamic Structure: A three-dimensional framework filling the cytoplasm composed of:
- Actin filaments (microfilaments)
- Intermediate filaments
- Microtubules

Structure:
- Diameter: 5-7 nm
- Composed of double-stranded helix of globular G-actin subunits.
- G-actin subunits added to the plus end and removed from the minus end during treadmilling (ATP-bound G-actin adds to filament, ADP-bound G-actin is released).
Function: Enable motility and contraction in cells.

Under the Plasma Membrane: Most actin microfilaments reside just beneath the plasma membrane, forming the cell cortex.
Microvilli Formation: Actin filaments form the structural core of microvilli, enhancing surface area for absorption, particularly in epithelial cells of the intestine and kidneys.
Muscle Contraction: In muscle cells, actin works with myosin (a motor protein) to facilitate contraction.
Cargo Transport: Actin filaments assist in moving vesicles and organelles across the cell.
Contractile Ring in Cell Division: During mitosis and meiosis, actin and myosin form a contractile ring to separate daughter cells.
Cell-to-Cell Junctions: In epithelial tissues, actin is integral to forming tight junctions (zonula occludens) and adherens junctions, connecting cells via cadherins.
Focal Adhesions: Dynamic structures that facilitate attachment of cells to the extracellular matrix, crucial for migration.

Mechanism: Involves actin polymerization forming lamellipodia (broad) and filopodia (thin) at the leading edge, establishing focal adhesions and enabling cell forward movement via depolymerization at the trailing edge.

Properties: Toughest and most stable component of the cytoskeleton, approximately 10 nm in diameter. They do not undergo rapid polymerization/depolymerization.
Function: Enable cells to withstand mechanical stress, form networks throughout the cytoplasm, and anchor to the plasma membrane at junctions.

Protein Composition: Composed of diverse, tissue-specific protein subunits. Assembled from monomers forming dimers, followed by tetra- and multi-layered bundles.
Categories: Intermediate filaments can be cytoplasmic (keratin, vimentin, desmin, GFAP in astrocytes) or nuclear (lamins in the nuclear envelope).
- Keratin: Present in epithelial cells, aids in structural integrity and protection.
- Vimentin: Found in connective tissue; Desmin: Found in muscle cells; Neurofilaments: Present in neurons.

Cancer Metastasis: The type of intermediate filaments present can indicate the origin tissue type of tumor cells, aiding in cancer diagnosis.

Overview: Present in all eukaryotic cells as long hollow tubes (25 nm). Composed of heterodimers of alpha and beta tubulin.
Function: Serve as tracks for intracellular transport, and are integral to cilia, flagella, and the mitotic spindle.

Structure: Each microtubule has a plus (+) and minus (-) end, with dynamics governed by GTP-bound tubulin addition at the plus end.
Microtubule-Organizing Centers: Centrosomes and basal bodies act as nucleating sites for microtubule polymerization.

Contains two centrioles arranged at right angles, surrounded by pericentriolar material, aiding in microtubule growth initiation via the gamma-tubulin ring complex.

Intracellular Transport: Motor proteins like kinesin and dynein facilitate the directed movement of vesicles and organelles.
Cilia and Flagella Formation: Cilia and flagella are organized into a 9+2 structure for movement, with basal bodies functioning as their anchors.

Mechanism: Dynein arms between doublets enable sliding movement, resulting in bending motions facilitated by nexin connections.

Anti-Cancer Drugs: Compounds like colchicine and taxol inhibit microtubule polymerization/depolymerization to prevent cancer cell division.
Gout Treatment: Colchicine is used to reduce inflammation in gout by inhibiting leukocyte movement.

Further reading on cytoskeleton can be found in "Junquiera’s Basic Histology," Chapter 2, for a deeper understanding of the cytoskeletal components and their functions.