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Updated: Feb 13 2022

Microtubules

  • Overview
    • Introduction
      • cellular structural protein with a hollow tubular structure
    • Structure
      • composed of polymerized dimers of α- and β-tubulin
        • each dimer has 2 GTP molecules bound
      • constant assembly (slow) and disassembly (fast)
        • clinical importance
          • Chédiak–Higashi syndrome (CHS)
            • etiology
              • a disease caused by a microtubule polymerization defect
            • resulting in decreased chemotaxis, degranulation, phagocytosis
            • AR inheritance
            • presentation
              • recurrent pyogenic infections
                • particularly S. aureus
              • partial albinism
              • peripheral neuropathy
    • Function
      • component of many important cellular structures
        • cilia
          • 9+2 arrangement of microtubules
          • axonemal dynein
            • ATPase that attaches the peripheral 9 doublets
            • causes bending of cilium by binding differentially to doublets
          • also forms the core of flagella
          • clinical importance
            • Kartagener syndrome
              • immotile cilia disease
              • cause
              • presentation
                • male and female infertility
                  • sperm are immotile (no functional flagellar tail)
                  • Fallopian tubes cannot sweep egg and sperm towards each other
                • bronchiectasis
                • recurrent sinusitis
                  • mucus with bacteria and particles cannot be removed
                • associated with situs inversus
        • mitotic spindles
        • molecular motor proteins
          • mediates intracellular transport
          • 2 types
            • kinesin
              • cell center → periphery
              • anterograde to microtubule
              • e.g. transports neurotransmitter vesicles down axon towards synapse
              • also transports Herpes zoster virus particles from the dorsal root ganglion during reactivation as shingles
            • dynein
              • periphery → cell center
              • retrograde to microtubule
              • e.g. lipid transport from synapse back to Golgi apparatus
    • Pharmacologic importance
      • mebendazole
        • class: antihelminthic
        • mechanism of action
          • microtubule synthesis in worms
      • griseofulvin
        • class: antifungal
        • mechanism of action
          • deposits in new keratin and disrupts microtubule polymerization
        • uses
          • active against dermatophytes only
      • vincristine/vinblastine
        • class: anti-cancer
        • mechanism of action
          • ↓ microtubule polymerization
            • inhibits mitosis
        • side effects
          • peripheral neuritis
          • areflexia
          • myelosuppression
      • paclitaxel (taxol)
        • class: anti-breast cancer
        • mechanism
          • ↑ stability of microtubule and does not allow disassembly
            • inhibits mitosis
      • colchicine
        • class: anti-gout
        • mechanism of action
          • binds free tubulin
          • ↓ microtubule polymerization
            • inhibits leukocyte/granulocyte migration
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