title: FAK promotes recruitment of talin to nascent adhesions to control cell motility.
abstract: Cell migration is a dynamic process that involves the continuous formation, maturation, and turnover of matrix-cell adhesion sites. New (nascent) adhesions form at the protruding cell edge in a tension-independent manner and are comprised of integrin receptors, signaling, and cytoskeletal-associated proteins. Integrins recruit focal adhesion kinase (FAK) and the cytoskeletal protein talin to nascent adhesions. Canonical models support a role for talin in mediating FAK localization and activation at adhesions. Here, alternatively, we show that FAK promotes talin recruitment to nascent adhesions occurring independently of talin binding to β1 integrins. The direct binding site for talin on FAK was identified, and a point mutation in FAK (E1015A) prevented talin association and talin localization to nascent adhesions but did not alter integrin-mediated FAK recruitment and activation at adhesions. Moreover, FAK E1015A inhibited cell motility and proteolytic talin cleavage needed for efficient adhesion dynamics. These results support an alternative linkage for FAK-talin interactions within nascent adhesions essential for the control of cell migration.
authors.affiliation: University of California San Diego, Moores Cancer Center, Department of Reproductive Medicine, La Jolla, CA 92093, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Lawson
authors.forename: Ssang-Taek
authors.initials: ST
authors.lastname: Lim
authors.forename: Sean
authors.initials: S
authors.lastname: Uryu
authors.forename: Xiao Lei
authors.initials: XL
authors.lastname: Chen
authors.forename: David A
authors.initials: DA
authors.lastname: Calderwood
authors.forename: David D
authors.initials: DD
authors.lastname: Schlaepfer
mesh_terms: D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002448:Cell Adhesion; D002465:Cell Movement; D006224:Cricetinae; D005434:Flow Cytometry; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D008856:Microscopy, Fluorescence; D021381:Protein Transport; D016608:Talin / Q000235:genetics / Q000378:metabolism*
chemical_list: D019012:Integrin beta1; D016608:Talin; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human