title: The C terminus of talin links integrins to cell cycle progression.
abstract: Integrins are cell adhesion receptors that sense the extracellular matrix (ECM) environment. One of their functions is to regulate cell fate decisions, although the question of how integrins initiate intracellular signaling is not fully resolved. In this paper, we examine the role of talin, an adapter protein at cell-matrix attachment sites, in outside-in signaling. We used lentiviral small hairpin ribonucleic acid to deplete talin in mammary epithelial cells. These cells still attached to the ECM in an integrin-dependent manner and spread. They had a normal actin cytoskeleton, but vinculin, paxillin, focal adhesion kinase (FAK), and integrin-linked kinase were not recruited to adhesion sites. Talin-deficient cells showed proliferation defects, and reexpressing a tail portion of the talin rod, but not its head domain, restored integrin-mediated FAK phosphorylation, suppressed p21 expression, and rescued cell cycle. Thus, talin recruits and activates focal adhesion proteins required for proliferation via the C terminus of its rod domain. Our study reveals a new function for talin, which is to link integrin adhesions with cell cycle progression.
authors: Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester M13 9PT, England, UK.
authors: Pengbo
authors: P
authors: Wang
authors: Christoph
authors: C
authors: Ballestrem
authors: Charles H
authors: CH
authors: Streuli
mesh_terms: D000818:Animals; D002453:Cell Cycle; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D016608:Talin / Q000235:genetics* / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism
chemical_list: D016023:Integrins; D051419:Paxillin; C518832:TLN1 protein, human; D016608:Talin; D016596:Vinculin; D051416:Focal Adhesion Protein-Tyrosine Kinases