Arginylation-dependent regulation of a proteolytic product of talin is essential for cell-cell adhesion.
Talin is a large scaffolding molecule that plays a major role in integrin-dependent cell-matrix adhesion. A role for talin in cell-cell attachment through cadherin has never been demonstrated, however. Here, we identify a novel calpain-dependent proteolytic cleavage of talin that results in the release of a 70-kD C-terminal fragment, which serves as a substrate of posttranslational arginylation. The intracellular levels of this fragment closely correlated with the formation of cell-cell adhesions, and this fragment localized to cadherin-containing cell-cell contacts. Moreover, reintroduction of this fragment rescued the cell-cell adhesion defects in arginyltransferase (Ate1) knockout cells, which normally have a very low level of this fragment. Arginylation of this fragment further enhanced its ability to rescue cell-cell adhesion formation. In addition, arginylation facilitated its turnover, suggesting a dual role of arginylation in its intracellular regulation. Thus, our work identifies a novel proteolytic product of talin that is regulated by arginylation and a new role of talin in cadherin-dependent cell-cell adhesion.
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Fangliang
F
Zhang
Sougata
S
Saha
Anna
A
Kashina
D019881:Aminoacyltransferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002154:Calpain / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D059748:Proteolysis; D016608:Talin / Q000235:genetics / Q000378:metabolism*
D015820:Cadherins; D016608:Talin; C496077:Tln1 protein, mouse; D001120:Arginine; D019881:Aminoacyltransferases; C019727:arginyltransferase; D002154:Calpain