title: Paxillin-dependent stimulation of microtubule catastrophes at focal adhesion sites.
abstract: An organized microtubule array is essential for the polarized motility of fibroblasts. Dynamic microtubules closely interact with focal adhesion sites in migrating cells. Here, we examined the effect of focal adhesions on microtubule dynamics. We observed that the probability of microtubule catastrophes (transitions from growth to shrinkage) was seven times higher at focal adhesions than elsewhere. Analysis of the dependence between the microtubule growth rate and catastrophe probability throughout the cytoplasm revealed that a nonspecific (mechanical or spatial) factor provided a minor contribution to the catastrophe induction by decreasing microtubule growth rate at adhesions. Strikingly, at the same growth rate, the probability of catastrophes was significantly higher at adhesions than elsewhere, indicative of a site-specific biochemical trigger. The observed catastrophe induction occurred at adhesion domains containing the scaffolding protein paxillin that has been shown previously to interact with tubulin. Furthermore, replacement of full-length paxillin at adhesion sites by microinjected paxillin LIM2-LIM3 domains suppressed microtubule catastrophes exclusively at adhesions. We suggest that paxillin influences microtubule dynamics at focal adhesions by serving as a scaffold for a putative catastrophe factor and/or regulating its exposure to microtubules.
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Andrey
authors.initials: A
authors.lastname: Efimov
authors.forename: Natalia
authors.initials: N
authors.lastname: Schiefermeier
authors.forename: Ilya
authors.initials: I
authors.lastname: Grigoriev
authors.forename: Ryoma
authors.initials: R
authors.lastname: Ohi
authors.forename: Michael C
authors.initials: MC
authors.lastname: Brown
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Turner
authors.forename: J Victor
authors.initials: JV
authors.lastname: Small
authors.forename: Irina
authors.initials: I
authors.lastname: Kaverina
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000378:metabolism; D006054:Goldfish; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D051419:Paxillin / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D003598:Cytoskeletal Proteins; D051419:Paxillin; D005982:Glutathione Transferase