Functional differences between kindlin-1 and kindlin-2 in keratinocytes.

Journal of Cell Science
Aditi BandyopadhyaySrikala Raghavan

Abstract

Integrin-β1-null keratinocytes can adhere to fibronectin through integrin αvβ6, but form large peripheral focal adhesions and exhibit defective cell spreading. Here we report that, in addition to the reduced avidity of αvβ6 integrin binding to fibronectin, the inability of integrin β6 to efficiently bind and recruit kindlin-2 to focal adhesions directly contributes to these phenotypes. Kindlins regulate integrins through direct interactions with the integrin-β cytoplasmic tail and keratinocytes express kindlin-1 and kindlin-2. Notably, although both kindlins localize to focal adhesions in wild-type cells, only kindlin-1 localizes to the integrin-β6-rich adhesions of integrin-β1-null cells. Rescue of these cells with wild-type and chimeric integrin constructs revealed a correlation between kindlin-2 recruitment and cell spreading. Furthermore, despite the presence of kindlin-1, knockdown of kindlin-2 in wild-type keratinocytes impaired cell spreading. Our data reveal unexpected functional consequences of differences in the association of two homologous kindlin isoforms with two closely related integrins, and suggest that despite their similarities, different kindlins are likely to have unique functions.

References

Nov 1, 2005·Cancer Metastasis Reviews·C Brakebusch, R Fässler
Sep 22, 2006·Journal of Cell Science·Jonathan D HumphriesMartin J Humphries
Aug 3, 2007·Nature Cell Biology·Ronen Zaidel-BarBenjamin Geiger
Feb 19, 2008·Nature Medicine·Markus MoserReinhard Fässler
May 7, 2008·The Journal of Cell Biology·Yan-Qing MaEdward F Plow
May 17, 2008·Genes & Development·Eloi MontanezReinhard Fässler
Nov 11, 2008·EMBO Reports·Hannu LarjavaChuanyue Wu
Jan 2, 2009·Journal of Cell Science·David S Harburger, David A Calderwood
Feb 26, 2009·Genes & Development·Kyle R LegateReinhard Fässler
May 16, 2009·Science·Markus MoserReinhard Fässler
Jun 26, 2009·Current Opinion in Hematology·Edward F PlowTatiana Byzova
Aug 19, 2009·Developmental Cell·Sara A Wickström, Reinhard Fässler
Sep 22, 2009·Trends in Cell Biology·Alexander MevesReinhard Fässler
Oct 27, 2009·The International Journal of Biochemistry & Cell Biology·J E Lai-CheongJ A McGrath
Mar 17, 2010·Blood·Nikolay L MalininTatiana V Byzova
Jul 2, 2010·Journal of Cell Science·Esra KaraköseReinhard Fässler
Sep 24, 2010·The Journal of Investigative Dermatology·Yinghong HeCristina Has
Mar 2, 2011·The American Journal of Pathology·Yinghong HeCristina Has
Mar 23, 2011·Cold Spring Harbor Perspectives in Biology·Sara A WickströmReinhard Fässler

❮ Previous
Next ❯

Citations

Jan 31, 2014·Frontiers of Medicine·Feng YeMark H Ginsberg
Jul 19, 2013·Nature Reviews. Molecular Cell Biology·David A CalderwoodDavid R Critchley
Jun 19, 2013·PloS One·Coert MargadantArnoud Sonnenberg
Oct 4, 2014·Molecular BioSystems·Sampo KukkurainenVesa P Hytönen
Mar 7, 2014·The Journal of Biological Chemistry·Paul FitzpatrickArarat J Ablooglu
Nov 28, 2018·Journal of Experimental & Clinical Cancer Research : CR·Paula AzorinKeltouma Driouch
Jul 18, 2019·Physiological Reviews·Michael BachmannBernhard Wehrle-Haller
Jan 6, 2016·Journal of Cell Science·Emanuel RognoniReinhard Fässler
Apr 6, 2016·The Journal of Cell Biology·Kamila BledzkaEdward F Plow
Mar 13, 2014·The Journal of Pathology·Yinghong HeCristina Has
Apr 23, 2017·Cell and Tissue Research·Cristina Has, Yinghong He
Jun 18, 2020·The Journal of Biological Chemistry·Yasmin A KadryDavid A Calderwood
Aug 25, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Alba ZuidemaArnoud Sonnenberg
Nov 12, 2013·Cell Communication & Adhesion·Samarth Hegde, Srikala Raghavan
Apr 1, 2014·Nature Medicine·Emanuel RognoniReinhard Fässler
Oct 30, 2013·The Journal of Biological Chemistry·Nina N BrahmeDavid A Calderwood
Aug 3, 2014·Journal of Cell Science·Clotilde Huet-CalderwoodDavid A Calderwood

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.