The C terminus of talin links integrins to cell cycle progression
- PMID: 22042621
- PMCID: PMC3206343
- DOI: 10.1083/jcb.201104128
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.
Figures
Similar articles
-
Mapping in vivo associations of cytoplasmic proteins with integrin beta 1 cytoplasmic domain mutants.Mol Biol Cell. 1995 Feb;6(2):151-60. doi: 10.1091/mbc.6.2.151. Mol Biol Cell. 1995. PMID: 7540435 Free PMC article.
-
Integrin adhesions: who's on first? What's on second? Connections between FAK and talin.Cell Adh Migr. 2012 Jul-Aug;6(4):302-6. doi: 10.4161/cam.20488. Epub 2012 Jul 1. Cell Adh Migr. 2012. PMID: 22983197 Free PMC article.
-
Talin requires beta-integrin, but not vinculin, for its assembly into focal adhesion-like structures in the nematode Caenorhabditis elegans.Mol Biol Cell. 1996 Aug;7(8):1181-93. doi: 10.1091/mbc.7.8.1181. Mol Biol Cell. 1996. PMID: 8856663 Free PMC article.
-
Mechanisms of talin-dependent integrin signaling and crosstalk.Biochim Biophys Acta. 2014 Feb;1838(2):579-88. doi: 10.1016/j.bbamem.2013.07.017. Epub 2013 Jul 24. Biochim Biophys Acta. 2014. PMID: 23891718 Free PMC article. Review.
-
Integrin signalling at a glance.J Cell Sci. 2009 Jan 15;122(Pt 2):159-63. doi: 10.1242/jcs.018093. J Cell Sci. 2009. PMID: 19118207 Free PMC article. Review. No abstract available.
Cited by
-
Relief of talin autoinhibition triggers a force-independent association with vinculin.J Cell Biol. 2020 Jan 6;219(1):e201903134. doi: 10.1083/jcb.201903134. J Cell Biol. 2020. PMID: 31816055 Free PMC article.
-
The tale of two talins - two isoforms to fine-tune integrin signalling.FEBS Lett. 2018 Jun;592(12):2108-2125. doi: 10.1002/1873-3468.13081. Epub 2018 May 18. FEBS Lett. 2018. PMID: 29723415 Free PMC article. Review.
-
The Integrin-Mediated ILK-Parvin-αPix Signaling Axis Controls Differentiation in Mammary Epithelial Cells.J Cell Physiol. 2016 Nov;231(11):2408-17. doi: 10.1002/jcp.25390. Epub 2016 Jun 10. J Cell Physiol. 2016. PMID: 27019299 Free PMC article.
-
Vinculin regulates the recruitment and release of core focal adhesion proteins in a force-dependent manner.Curr Biol. 2013 Feb 18;23(4):271-81. doi: 10.1016/j.cub.2013.01.009. Epub 2013 Jan 31. Curr Biol. 2013. PMID: 23375895 Free PMC article.
-
Postnatal Loss of Kindlin-2 Leads to Progressive Heart Failure.Circ Heart Fail. 2016 Aug;9(8):10.1161/CIRCHEARTFAILURE.116.003129 e003129. doi: 10.1161/CIRCHEARTFAILURE.116.003129. Circ Heart Fail. 2016. PMID: 27502369 Free PMC article.
References
-
- Barsukov I.L., Prescot A., Bate N., Patel B., Floyd D.N., Bhanji N., Bagshaw C.R., Letinic K., Di Paolo G., De Camilli P., et al. 2003. Phosphatidylinositol phosphate kinase type 1gamma and beta1-integrin cytoplasmic domain bind to the same region in the talin FERM domain. J. Biol. Chem. 278:31202–31209 10.1074/jbc.M303850200 - DOI - PubMed
-
- Cabodi S., Tinnirello A., Di Stefano P., Bisarò B., Ambrosino E., Castellano I., Sapino A., Arisio R., Cavallo F., Forni G., et al. 2006. p130Cas as a new regulator of mammary epithelial cell proliferation, survival, and HER2-neu oncogene-dependent breast tumorigenesis. Cancer Res. 66:4672–4680 10.1158/0008-5472.CAN-05-2909 - DOI - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Miscellaneous