Microtubule: Difference between revisions

Dynamic instability of microtubules is also required for the migration of most mammalian cells that crawl.<ref name="MikhailovGundersen1998">{{cite journal |vauthors = Mikhailov A, Gundersen GG |title = Relationship between microtubule dynamics and lamellipodium formation revealed by direct imaging of microtubules in cells treated with nocodazole or taxol |journal = Cell Motility and the Cytoskeleton |volume = 41 | issue = 4 |pages = 325–40| year = 1998 |pmid = 9858157 |doi = 10.1002/(SICI)1097-0169(1998)41:4<325::AID-CM5>3.0.CO;2-D }}</ref> Dynamic microtubules regulate the levels of key [[G-proteins]] such as [[RhoA]]<ref name="Ren1999">{{cite journal |vauthors = Ren XD, Kiosses WB, Schwartz MA |title = Regulation of the small GTP-binding protein Rho by cell adhesion and the cytoskeleton |journal = The EMBO Journal |volume = 18 |issue = 3 |pages = 578–85 |date = February 1999 |pmid = 9927417 |pmc = 1171150 |doi = 10.1093/emboj/18.3.578 }}</ref> and [[Rac1]],<ref name="Waterman-StorerWorthylake1999">{{cite journal |vauthors = Waterman-Storer CM, Worthylake RA, Liu BP, Burridge K, Salmon ED |title = Microtubule growth activates Rac1 to promote lamellipodial protrusion in fibroblasts |journal = Nature Cell Biology |volume = 1 |issue = 1 |pages = 45–50 |date = May 1999 |pmid = 10559863 |doi = 10.1038/9018 |s2cid = 26321103 }}</ref> which regulate cell contractility and cell spreading. Dynamic microtubules are also required to trigger [[focal adhesion]] disassembly, which is necessary for migration.<ref>{{cite journal |vauthors = Ezratty EJ, Partridge MA, Gundersen GG |title = Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase |journal = Nature Cell Biology |volume = 7 |issue = 6 |pages = 581–90 |date = June 2005 |pmid = 15895076 |doi = 10.1038/ncb1262 |s2cid = 37153935 }}</ref> It has been found that microtubules act as “struts”"struts" that counteract the contractile forces that are needed for trailing edge retraction during cell movement. When microtubules in the trailing edge of cell are dynamic, they are able to remodel to allow retraction. When dynamics are suppressed, microtubules cannot remodel and, therefore, oppose the contractile forces.<ref name=pmid20696757/> The morphology of cells with suppressed microtubule dynamics indicate that cells can extend the front edge (polarized in the direction of movement), but have difficulty retracting their trailing edge.<ref name="ReferenceA">{{cite journal |vauthors = Ganguly A, Yang H, Sharma R, Patel KD, Cabral F |title = The role of microtubules and their dynamics in cell migration |journal = The Journal of Biological Chemistry |volume = 287 |issue = 52 |pages = 43359–69 |date = December 2012 |pmid = 23135278 |pmc = 3527923 |doi = 10.1074/jbc.M112.423905 |doi-access = free }}</ref> On the other hand, high drug concentrations, or microtubule mutations that depolymerize the microtubules, can restore cell migration but there is a loss of directionality. It can be concluded that microtubules act both to restrain cell movement and to establish directionality.