Molecular Motors and Cytoskeleton

Cytoskeleton Overview - Cell's Bony Framework

• Cell's dynamic internal scaffolding, crucial for structural integrity, intracellular transport, cell motility, and division.

• Composed of three main protein filament types.

• Key types compared:

⭐ Intermediate filaments are the most stable and least dynamic, providing tensile strength.

Microfilaments & Myosin - Actin's Muscle Hustle

• Actin (Microfilaments): Dynamic polymers of G-actin.
  • Polymerization: ATP-dependent, $G-actin + ATP \rightarrow F-actin + ADP + Pi$; forms polar filaments (+ fast, - slow ends).
  • Treadmilling: Net assembly at + end, disassembly at - end.
  • Key ABPs: Spectrin (RBC shape), Dystrophin (muscle integrity, links to sarcolemma), Arp2/3 (branched networks), Formins (unbranched filaments), Tropomyosin (regulates myosin binding).
• Myosins (Motor Proteins): ATP-dependent motors moving on actin.
  • Structure: Head (actin-binding, ATPase), neck (lever), tail (cargo/dimerization).
  • Types: Myosin II (muscle contraction, cytokinesis; bipolar filaments), Myosin V (vesicle transport; processive).

⭐ Dystrophin gene mutations cause DMD (severe, frameshift) & BMD (milder, in-frame).

Microtubules & Motors - Tubulin's Tiny Trucks

• Structure: α/β-tubulin dimers → protofilaments. Polarity: (+) & (-) ends. Dynamic instability (GTP cap crucial).
• MTOCs: Centrosomes (γ-TuRCs), Basal bodies.
• MAPs: Stabilizing proteins (e.g., Tau, MAP2) and destabilizing proteins (e.g., Katanin).
• Motor Proteins: Utilize ATP for movement along microtubules.
  • Kinesins: Mostly anterograde (to + end). 📌 Kinesin 'Kicks out' from cell center.
  • Dyneins: Retrograde (to - end). 📌 Dynein 'Drags in'. Cytoplasmic & Axonemal types.

Intermediate Filaments - Cell's Stress Ropes

• Strong, rope-like, non-polar filaments; provide high tensile strength. No intrinsic polarity, enzymatic activity, or motor protein tracks.
• Assembly: Monomers → Dimers → Tetramers → Protofilaments → Filament. | Type | Protein(s) | Tissue/Function | |--------|----------------------|-------------------------------------| | I & II | Keratins | Epithelia (mechanical strength) | | III | Vimentin, Desmin, GFAP | Mesenchyme, Muscle, Glia (structure)| | IV | Neurofilaments | Neurons (axonal caliber) | | V | Lamins | Nuclear envelope (nuclear support) |

⭐ Intermediate filament typing (e.g., cytokeratin for carcinomas, vimentin for sarcomas) is a cornerstone in tumor immunohistochemical diagnosis.

Cytoskeletal Pathologies - When Scaffolds Fail

• Microfilaments (Actin):
  • Duchenne/Becker Muscular Dystrophy: Dystrophin defect.
  • Listeria infection: Bacterial ActA protein hijacks actin.
• Microtubules:
  • Kartagener Syndrome (Primary Ciliary Dyskinesia): Dynein arm defect (cilia).
  • Alzheimer's Disease: Hyperphosphorylated Tau protein (tangles).
  • Charcot-Marie-Tooth Neuropathy: Kinesin motor protein defects.
  • Drugs: Vinca alkaloids (e.g., Vincristine; inhibit polymerization), Taxanes (e.g., Paclitaxel; stabilize). Colchicine (anti-gout; inhibits polymerization).
• Intermediate Filaments:
  • Epidermolysis Bullosa Simplex: Keratin defect (skin fragility).
  • Laminopathies (e.g., Progeria): Lamin A defect (premature aging).
  • Alexander Disease: GFAP defect (astrocytes).

⭐ Vinca alkaloids (Vincristine, Vinblastine) bind tubulin dimers, prevent microtubule polymerization, arresting cells in metaphase.

High‑Yield Points - ⚡ Biggest Takeaways

• Kinesin drives anterograde transport (to microtubule +end); Dynein drives retrograde (to -end).
• Myosin interacts with actin for muscle contraction, cytokinesis, and cell movement.
• Microtubules (tubulin) form cilia, flagella, mitotic spindles, and maintain cell shape.
• Intermediate filaments (e.g., keratins, lamins) provide tensile strength and structural integrity.
• Actin filaments (microfilaments) are crucial for cell motility, phagocytosis, and cytoplasmic streaming.
• Colchicine/Vinca alkaloids disrupt microtubules; Taxol stabilizes them. ATP hydrolysis fuels motor proteins.