A Rich1/Amot Complex Regulates the Cdc42 GTPase and Apical-Polarity Proteins in Epithelial Cells

Clark D. Wells, James P. Fawcett, Andreas Traweger, Yojiro Yamanaka, Marilyn Goudreault, Kelly Elder, Sarang Kulkarni, Gerald Gish, Cristina Virag, Caesar Lim, Karen Colwill, Andrei Starostine, Pavel Metalnikov, Tony Pawson

Research output: Contribution to journalArticle

245 Scopus citations

Abstract

Using functional and proteomic screens of proteins that regulate the Cdc42 GTPase, we have identified a network of protein interactions that center around the Cdc42 RhoGAP Rich1 and organize apical polarity in MDCK epithelial cells. Rich1 binds the scaffolding protein angiomotin (Amot) and is thereby targeted to a protein complex at tight junctions (TJs) containing the PDZ-domain proteins Pals1, Patj, and Par-3. Regulation of Cdc42 by Rich1 is necessary for maintenance of TJs, and Rich1 is therefore an important mediator of this polarity complex. Furthermore, the coiled-coil domain of Amot, with which it binds Rich1, is necessary for localization to apical membranes and is required for Amot to relocalize Pals1 and Par-3 to internal puncta. We propose that Rich1 and Amot maintain TJ integrity by the coordinate regulation of Cdc42 and by linking specific components of the TJ to intracellular protein trafficking.

Original languageEnglish (US)
Pages (from-to)535-548
Number of pages14
JournalCell
Volume125
Issue number3
DOIs
StatePublished - May 5 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Wells, C. D., Fawcett, J. P., Traweger, A., Yamanaka, Y., Goudreault, M., Elder, K., Kulkarni, S., Gish, G., Virag, C., Lim, C., Colwill, K., Starostine, A., Metalnikov, P., & Pawson, T. (2006). A Rich1/Amot Complex Regulates the Cdc42 GTPase and Apical-Polarity Proteins in Epithelial Cells. Cell, 125(3), 535-548. https://doi.org/10.1016/j.cell.2006.02.045