QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Research Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Nakamura, T. Articles by Akiyama, T. PubMed PubMed Citation Articles by Nakamura, T. Articles by Akiyama, T. Social Bookmarking                   What's this?

PX-RICS mediates ER-to-Golgi transport of the N-cadherin/β-catenin complex

¹ Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan; ² Department of Human Pathology and Departmen of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan; ³ Second Department of Surgery, Gunma University School of Medicine, Maebashi, Gunma 371-0034, Japan

Cadherins mediate Ca²⁺-dependent cell–cell adhesion. Efficient export of cadherins from the endoplasmic reticulum (ER) is known to require complex formation with β-catenin. However, the molecular mechanisms underlying this requirement remain elusive. Here we show that PX-RICS, a β-catenin-interacting GTPase-activating protein (GAP) for Cdc42, mediates ER-to-Golgi transport of the N-cadherin/β-catenin complex. Knockdown of PX-RICS expression induced the accumulation of the N-cadherin/β-catenin complex in the ER and ER exit site, resulting in a decrease in cell–cell adhesion. PX-RICS was also required for ER-to-Golgi transport of the fibroblast growth factor-receptor 4 (FGFR4) associated with N-cadherin. PX-RICS-mediated ER-to-Golgi transport was dependent on its interaction with β-catenin, phosphatidylinositol-4-phosphate (PI4P), Cdc42, and its novel binding partner -aminobutyric acid type A receptor-associated protein (GABARAP). These results suggest that PX-RICS ensures the efficient entry of the N-cadherin/β-catenin complex into the secretory pathway, and thereby regulates the amount of N-cadherin available for cell adhesion and FGFR4-mediated signaling.

[Keywords: N-cadherin; β-catenin; PX-RICS; GABARAP; PI4P; Cdc42]]

Received November 7, 2007; revised version accepted March 4, 2008.

E-MAIL nakamura{at}iam.u-tokyo.ac.jp; FAX 81-3-5841-8482.

⁵ E-MAIL akiyama{at}iam.u-tokyo.ac.jp; FAX 81-3-5841-8482.

Supplemental material is available at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1632308.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?