title: The role of microtubules and their dynamics in cell migration.
abstract: Although microtubules have long been implicated in cell locomotion, the mechanism of their involvement remains controversial. Most studies have concluded that microtubules play a positive role by regulating actin polymerization, transporting membrane vesicles to the leading edge, and/or facilitating the turnover of adhesion plaques. Here we used wild-type and mutant CHO cell lines with alterations in tubulin to demonstrate that microtubules can also act to restrain cell motility. Tubulin mutations or low concentrations of drugs that suppress microtubule dynamics without affecting the amount of microtubule polymer inhibited the rate of migration by preventing microtubule reorganization in the trailing portion of the cells where the more dynamic microtubules are normally found. Under these conditions, cells along the edge of a wound still extended lamellipodia and elongated toward the wound but were inhibited in their ability to retract their tails, thus retarding forward progress. The idea that microtubules normally act to restrain cell locomotion was confirmed by treating cells with high concentrations of nocodazole to depolymerize the microtubule network. In the absence of microtubules, wild-type CHO and HeLa cells could still move at near normal speeds, but the movement became more random. We conclude that microtubules act both to restrain cell movement and to establish directionality.
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Medical School, Houston, Texas 77030, USA.
authors.forename: Anutosh
authors.initials: A
authors.lastname: Ganguly
authors.forename: Hailing
authors.initials: H
authors.lastname: Yang
authors.forename: Ritu
authors.initials: R
authors.lastname: Sharma
authors.forename: Kamala D
authors.initials: KD
authors.lastname: Patel
authors.forename: Fernando
authors.initials: F
authors.lastname: Cabral
mesh_terms: D000818:Animals; D016466:CHO Cells; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D011554:Pseudopodia / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D014404:Tubulin; D050257:Tubulin Modulators; D015739:Nocodazole