Arginylation-dependent regulation of a proteolytic product of talin is essential for cell-cell adhesion

Fangliang Zhang, Sougata Saha, Anna Kashina

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)819-836
Number of pages18
JournalJournal of Cell Biology
Volume197
Issue number6
DOIs
StatePublished - Jun 11 2012

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Talin
Cell Adhesion
Cadherins
arginyltransferase
Cell-Matrix Junctions
Calpain
Integrins

ASJC Scopus subject areas

  • Cell Biology

Cite this

Arginylation-dependent regulation of a proteolytic product of talin is essential for cell-cell adhesion. / Zhang, Fangliang; Saha, Sougata; Kashina, Anna.

In: Journal of Cell Biology, Vol. 197, No. 6, 11.06.2012, p. 819-836.

Research output: Contribution to journalArticle

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AB - 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.

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