Arrestins regulate cell spreading and motility via focal adhesion dynamics
Year: 2014
Type: article
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.
Source: Molecular Biology of the Cell
Institutions: Vanderbilt University, National Institutes of Health
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
Funders: U.S. Department of Veterans Affairs, American Heart Association, Vanderbilt University, Vanderbilt University Medical Center, National Institutes of Health, National Institute on Drug Abuse, National Eye Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1149166549, Eunice Kennedy Shriver Intellectual and Developmental Disability Research Center, Spatial Organization of Cytoskeletal Asymmetry, Cortactin function in lamellipodial protrusion, G150953014, Betal Integrin and Renal Tubulogenesis, G1766553809, G209152575, G2304076072, Training in Pharmacological Sciences, G2529513676, G2532530556, The role of receptor desensitization machinery in psychostimulant addiction, G2910294509, G2940777275, G3166704001, Structure Function Analysis of Integrins alpha1beta1 and alpha2beta2, G3416501184, G3487880643, G3515409131, G35732448, G3722609264, G3865556588, G3965739558, G3989539122, Arrestin interactions with non-receptor binding partners, Vanderbilt Mouse Metabolic Phenotyping Center, G4320917349, G4416941928, G4513176822, Initiative for Maximizing Student Development, G5132347646, G5710306463, G5853943267, G6297262231, G6389250872, Multiscale Modeling of ECM-tumor interactions in Breast Cancer, Exocytic pathways in HNSCC progression, G7134506048, G718647164, G7220527126, G7390749777, G7444061393, Diabetes Research and Training Center, G8151396209, G8251680236, Signaling regulation in the striatum in Parkinson's disease, G8391480415, G8410895666, Conformational regulation of arrestin-mediated signaling, G8981724719, G9000002043, G9000060478, G9000081609, G9000106052, G9000135199, G9000159340, Molecular and Cellular Basis for Digestive Diseases, Integrated Biological Systems Training in Oncology, Cancer Center Support Grant, Structure-function studies of visual arrestin, Vanderbilt Diabetes Research Center, Core Grant in Vision Research, The Laminin Receptors in Kidney Disease
OpenAlex ID: W2147874971