Microtubules

  • Cylindrical outer structure composed of a helical array of polymerized heterodimers of α- and β-tubulin.
  • Each dimer has 2 GTP bound.
  • Incorporated into flagella, cilia, mitotic spindles.
  • Grows slowly, collapses quickly.
  • Also involved in slow axoplasmic transport in neurons.
  • Molecular motor proteins—transport cellular cargo toward opposite ends of microtubule tracks.
    • Dynein—retrograde to microtubule (+ −).
    • Kinesin—anterograde to microtubule (− +).
  • Negative end Near Nucleus. Positive end Points to Periphery
  • Drugs that act on microtubules (Microtubules Get Constructed Very Poorly):
    • Mebendazole (antihelminthic)
    • Griseofulvin (antifungal)
    • Colchicine (antigout)
    • Vincristine/Vinblastine (anticancer)
    • Paclitaxel (anticancer)
  • Cilia structure
    • 9 doublet + 2 singlet arrangement of microtubules (A).
    • Basal body (base of cilium below cell membrane) consists of 9 microtubule triplets B with no central microtubules.
    • Axonemal dynein—ATPase that links peripheral 9 doublets and causes bending of cilium by differential sliding of doublets.
    • Gap junctions enable coordinated ciliary movement.
  • Kartagener syndrome (1° ciliary dyskinesia)
    • immotile cilia due to a dynein arm defect.
    • Autosomal recessive.
    • Results in male and female fertility due to immotile sperm (compared to cystic fibrosis, which has an absent vas deferens) and dysfunctional fallopian tube cilia, respectively;
    • risk of ectopic pregnancy.
    • Can cause impaired mucociliary clearance, bronchiectasis, digital clubbing recurrent sinusitis, nasal polyps, chronic ear infections, conductive hearing loss, and situs inversus (eg, dextrocardia on CXR (C)).
    • (Kartagener’s restaurant: take-out only, there’s no dynein “dine-in”).
    • Diagnosis: Low nasal nitric oxide levels. Bronchoscopy and electron microscopic visualization of ciliary abnormalities. Genetic testing.

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