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 dynein arm defect 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