title: Arrestins regulate cell spreading and motility via focal adhesion dynamics.
abstract: Focal adhesions (FAs) play a key role in cell attachment, and their timely disassembly is required for cell motility. Both microtubule-dependent targeting and recruitment of clathrin are critical for FA disassembly. Here we identify nonvisual arrestins as molecular links between microtubules and clathrin. Cells lacking both nonvisual arrestins showed excessive spreading on fibronectin and poly-d-lysine, increased adhesion, and reduced motility. The absence of arrestins greatly increases the size and lifespan of FAs, indicating that arrestins are necessary for rapid FA turnover. In nocodazole washout assays, FAs in arrestin-deficient cells were unresponsive to disassociation or regrowth of microtubules, suggesting that arrestins are necessary for microtubule targeting-dependent FA disassembly. Clathrin exhibited decreased dynamics near FA in arrestin-deficient cells. In contrast to wild-type arrestins, mutants deficient in clathrin binding did not rescue the phenotype. Collectively the data indicate that arrestins are key regulators of FA disassembly linking microtubules and clathrin.
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, TN 37232.
authors.forename: Whitney M
authors.initials: WM
authors.lastname: Cleghorn
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Branch
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, TN 37232.
authors.forename: Seunghyi
authors.initials: S
authors.lastname: Kook
authors.affiliation: Department of Cell Biology, Vanderbilt University, Nashville, TN 37232.
authors.forename: Christopher
authors.initials: C
authors.lastname: Arnette
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN 37232.
authors.forename: Nada
authors.initials: N
authors.lastname: Bulus
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN 37232.
authors.forename: Roy
authors.initials: R
authors.lastname: Zent
authors.affiliation: Department of Cell Biology, Vanderbilt University, Nashville, TN 37232.
authors.forename: Irina
authors.initials: I
authors.lastname: Kaverina
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, TN 37232.
authors.forename: Eugenia V
authors.initials: EV
authors.lastname: Gurevich
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232.
authors.forename: Alissa M
authors.initials: AM
authors.lastname: Weaver
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, TN 37232 vsevolod.gurevich@vanderbilt.edu.
authors.forename: Vsevolod V
authors.initials: VV
authors.lastname: Gurevich
mesh_terms: D000818:Animals; D019390:Arrestins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement; D005347:Fibroblasts; D022001:Focal Adhesions; D051379:Mice
chemical_list: D019390:Arrestins