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

Vol. 18, Issue 5, 1710-1722, May 2007

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E06-07-0629v1 18/5/1710    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yu, C.-Y. Articles by Jou, T.-S. Search for Related Content PubMed PubMed Citation Articles by Yu, C.-Y. Articles by Jou, T.-S.

A Bipartite Signal Regulates the Faithful Delivery of Apical Domain Marker Podocalyxin/Gp135

Chun-Ying Yu^*, Jen-Yau Chen^*, Yu-Yu Lin^*, Kuo-Fang Shen^*, Wei-Ling Lin^*, Chung-Liang Chien, Martin B.A. ter Beest, and Tzuu-Shuh Jou^*

*Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, 100 Taiwan; Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, 100 Taiwan; and Epithelial Pathobiology, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH 45267

Submitted July 24, 2006; Revised January 16, 2007; Accepted February 16, 2007
Monitoring Editor: Howard Riezman

Podocalyxin/Gp135 was recently demonstrated to participate in the formation of a preapical complex to set up initial polarity in MDCK cells, a function presumably depending on the apical targeting of Gp135. We show that correct apical sorting of Gp135 depends on a bipartite signal composed of an extracellular O-glycosylation–rich region and the intracellular PDZ domain–binding motif. The function of this PDZ-binding motif could be substituted with a fusion construct of Gp135 with Ezrin-binding phosphoprotein 50 (EBP50). In accordance with this observation, EBP50 binds to newly synthesized Gp135 at the Golgi apparatus and facilitates oligomerization and sorting of Gp135 into a clustering complex. A defective connection between Gp135 and EBP50 or EBP50 knockdown results in a delayed exit from the detergent-resistant microdomain, failure of oligomerization, and basolateral missorting of Gp135. Furthermore, the basolaterally missorted EBP50-binding defective mutant of Gp135 was rapidly retrieved via a PKC-dependent mechanism. According to these findings, we propose a model by which a highly negative charged transmembrane protein could be packed into an apical sorting platform with the aid of its cytoplasmic partner EBP50.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Tzuu-Shuh Jou (jouts{at}med.mc.ntu.edu.tw)

This article has been cited by other articles:

				J. M. Torkko, A. Manninen, S. Schuck, and K. Simons Depletion of apical transport proteins perturbs epithelial cyst formation and ciliogenesis J. Cell Sci., April 15, 2008; 121(8): 1193 - 1203. [Abstract] [Full Text] [PDF]