Par3 integrates Tiam1 and phosphatidylinositol 3-kinase signaling to change apical membrane identity

Ruch, T. R., Bryant, D. M. , Mostov, K. E., Engel, J. N. and Yap, A. (2017) Par3 integrates Tiam1 and phosphatidylinositol 3-kinase signaling to change apical membrane identity. Molecular Biology of the Cell, 28(2), pp. 252-260. (doi: 10.1091/mbc.E16-07-0541) (PMID:27881661)

Abstract

Pathogens can alter epithelial polarity by recruiting polarity proteins to the apical membrane, but how a change in protein localization is linked to polarity disruption is not clear. In this study, we used chemically induced dimerization to rapidly relocalize proteins from the cytosol to the apical surface. We demonstrate that forced apical localization of Par3, which is normally restricted to tight junctions, is sufficient to alter apical membrane identity through its interactions with phosphatidylinositol 3-kinase (PI3K) and the Rac1 guanine nucleotide exchange factor Tiam1. We further show that PI3K activity is required upstream of Rac1, and that simultaneously targeting PI3K and Tiam1 to the apical membrane has a synergistic effect on membrane remodeling. Thus, Par3 coordinates the action of PI3K and Tiam1 to define membrane identity, revealing a signaling mechanism that can be exploited by human mucosal pathogens.

• Item Type: Articles
• Additional Information: This project was funded by grants from the National Institutes of Health to J.E. (AI065902), D.M.B. (K99CA163535), and K.E.M. (DK074398 and DK091530). T.R. was supported by the National Institutes of Health (T32) and the Cystic Fibrosis Research Elizabeth Nash Memorial Fellowship.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bryant, Dr David
• Authors: Ruch, T. R., Bryant, D. M., Mostov, K. E., Engel, J. N., and Yap, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Molecular Biology of the Cell
• Publisher: American Society for Cell Biology
• ISSN: 1059-1524
• ISSN (Online): 1939-4586
• Published Online: 23 November 2016
• Copyright Holders: Copyright © 2017 Ruch et al.
• First Published: First published in Molecular Biology of the Cell 28(2): 252-260
• Publisher Policy: Reproduced under a Creative Commons License