U01.01.028 Microtubule

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Learning Objectives

  • Identify the biochemical structure of microtubules and their energy requirements.
  • Distinguish between Dynein and Kinesin motor proteins.
  • Recognize pathogens that exploit retrograde transport.
  • Master the list of microtubule-acting drugs and their clinical uses.

1. Microtubule Structure & Polarity

Microtubules are large, cylindrical structures composed of polymerized \alpha– and \beta-tubulin heterodimers. Each dimer is bound to two GTP molecules.

  • Polarity:
    • Negative (–) end: Located near the nucleus (at the centrosome).
    • Positive (+) end: Points toward the periphery (cell membrane).
  • Functions: Incorporated into flagella, cilia, and mitotic spindles; drives slow axoplasmic transport in neurons.

2. Molecular Motor Proteins

These motors carry cargo (vesicles, organelles) along the microtubule “highway.”

Motor Direction Clinical Significance
Dynein Retrograde (+ → –)
Periphery to Nucleus		 Used by Rabies, Polio, Tetanus toxin, and HSV to reach the neuronal cell body.
Kinesin Anterograde (– → +)
Nucleus to Periphery		 Used for HSV reactivation (moving from ganglion to skin) and nerve regeneration.

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3. Clinical Correlation: Pathogens & Nerve Repair

  • Viral Hijacking: Viruses such as rabies and HSV “ride” Dynein to enter the CNS. When HSV reactivates (e.g., cold sores), it switches to Kinesin to return to the skin.
  • Nerve Regeneration: Slow anterograde transport (kinesin-mediated) is the rate-limiting step when a peripheral nerve tries to regrow after an injury.

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4. Drugs acting on Microtubules

Mnemonic: Microtubules Get Constructed Very Terribly.

Drug Clinical Use
Mebendazole Antihelminthic (Pinworms, etc.)
Griseofulvin Antifungal
Colchicine Antigout (inhibits neutrophil migration)
Vinca alkaloids Anticancer (Vincristine, Vinblastine)
Taxanes Anticancer (Paclitaxel)

 

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