mcb104 handout week 8 (2)

mcb104 handout week 8 (2) - o The plus-end is free to grow...

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CYTOSKELETON: MICROTUBULES Microtubules : Roles: vesicle trafficking, chromosome segregation during cell division, cilia/flagella Composed of α and β -tubulin subunits o Heterodimers assemble into protofilaments, which form sheets of 13 protofilaments, and sheets wrap around to form hollow tubes Both subunits bind GTP, and β -tubulin has weak GTPase activity (which is not required for polymerization) o MTs are stabilized by GTP-bound β -tubulin, and destabilized by GDP-bound β -tubulin o GTP-bound β -tubulin subunits form a protective stabilizing cap at the plus-end Nucleation and growth of microtubules: MTs grow from Microtubule Organizing Centers (MTOCs) o e.g. centrosomes, spindle poles during cell division, basal bodies for cilia/flagella o MTOCs contain centrioles surrounded by pericentriolar material o The pericentriolar material contains γ -TURCs ( γ -tubulin ring complexes), which nucleate microtubule growth Like actin, microtubules are polarized, but the minus-end is MTOC-anchored and stabilized
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Unformatted text preview: o The plus-end is free to grow and shrink • Dynamic instability : MTs cycle between catastrophe (rapid depolymerization) and rescue (restarted polymerization) Microtubule-associated motors : kinesins, dyneins • Both are ATPases and are used to traffic vesicles and other cargo along MTs • Kinesins mostly move towards the plus-end, while dyneins move towards the minus-end Drugs that affect MTs: • Taxol stabilizes the cap of GTP-bound β-tubulin and promotes MT growth/stability • Colchicine promotes GTPase activity of β-tubulin, encouraging MT instability and depolymerization MAPs (Microtubule-associated proteins): • Kinesin-13 binds free dimers (reducing their concentration) and promotes GTP hydrolysis at the plus-end destabilizing • Stathmin/Op18 bends and destabilizes the plus-end • Katanin and Spastin sever MTs (promoting depolymerization: severed end has no GTP cap) • Lattice- & end-binding MAPs stabilize microtubules...
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