RPTPα controls epithelial adherens junctions, linking E-cadherin engagement to c-Src-mediated phosphorylation of cortactin

Truffi, Marta, Dubreuil, Veronique, Liang, Xuan, Vacaresse, Nathalie, Nigon, Fabienne, Han, Siew Ping, Yap, Alpha S., Gomez, Guillermo A. and Sap, Jan (2014) RPTPα controls epithelial adherens junctions, linking E-cadherin engagement to c-Src-mediated phosphorylation of cortactin. Journal of Cell Science, 127 11: 2420-2432. doi:10.1242/jcs.134379

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Author Truffi, Marta
Dubreuil, Veronique
Liang, Xuan
Vacaresse, Nathalie
Nigon, Fabienne
Han, Siew Ping
Yap, Alpha S.
Gomez, Guillermo A.
Sap, Jan
Title RPTPα controls epithelial adherens junctions, linking E-cadherin engagement to c-Src-mediated phosphorylation of cortactin
Journal name Journal of Cell Science   Check publisher's open access policy
ISSN 1477-9137
0021-9533
Publication date 2014-01-01
Sub-type Article (original research)
DOI 10.1242/jcs.134379
Open Access Status File (Publisher version)
Volume 127
Issue 11
Start page 2420
End page 2432
Total pages 13
Place of publication Cambridge, United Kingdom
Publisher Company of Biologists
Language eng
Subject 1307 Cell Biology
Abstract Epithelial junctions are fundamental determinants of tissue organization, subject to regulation by tyrosine phosphorylation. Homophilic binding of E-cadherin activates tyrosine kinases, such as Src, that control junctional integrity. Protein tyrosine phosphatases (PTPs) also contribute to cadherin-based adhesion and signaling, but little is known about their specific identity or functions at epithelial junctions. Here, we report that the receptor PTP RPTPα (human gene name PTPRA) is recruited to epithelial adherens junctions at the time of cell-cell contact, where it is in molecular proximity to E-cadherin. RPTPα is required for appropriate cadherin-dependent adhesion and for cyst architecture in three-dimensional culture. Loss of RPTPa impairs adherens junction integrity, as manifested by defective E-cadherin accumulation and peri-junctional F-actin density. These effects correlate with a role for RPTPa in cellular (c)-Src activation at sites of E-cadherin engagement. Mechanistically, RPTPα is required for appropriate tyrosine phosphorylation of cortactin, a major Src substrate and a cytoskeletal actin organizer. Expression of a phosphomimetic cortactin mutant in RPTPα-depleted cells partially rescues F-actin and E-cadherin accumulation at intercellular contacts. These findings indicate that RPTPa controls cadherinmediated signaling by linking homophilic E-cadherin engagement to cortactin tyrosine phosphorylation through c-Src.
Keyword Adherens junctions
C-Src
Cortactin
E-cadherin
Tyrosine phosphatase
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
 
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