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Originally published as MBC in Press, 10.1091/mbc.E06-11-0980 on March 1, 2007

Vol. 18, Issue 5, 1744-1755, May 2007

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The MAGUK Protein MPP7 Binds to the Polarity Protein hDlg1 and Facilitates Epithelial Tight Junction FormationFormula

Volker M. Stucke*, Evy Timmerman{dagger}, Joel Vandekerckhove{dagger}, Kris Gevaert{dagger}, and Alan Hall*,{ddagger}

*Medical Research Council Laboratory for Molecular Cell Biology, Cancer Research UK Oncogene and Signal Transduction Group, University College London, London WC1E 6BT, England; and {dagger}Department of Medical Protein Research, Flanders Interuniversity Institute for Biotechnology and Department of Biochemistry, Ghent University, B-9000 Ghent, Belgium

Submitted November 1, 2006; Revised January 16, 2007; Accepted February 15, 2007
Monitoring Editor: Ben Margolis

Three groups of evolutionarily conserved proteins have been implicated in the establishment of epithelial cell polarity: the apically-localized proteins of the Par (Par3-Par6-aPKC-Cdc42) and Crumbs groups (Crb3-PALS1-PATJ) and the basolaterally localized proteins of the Dlg group (Dlg1-Scribble-Lgl). During epithelial morphogenesis, these proteins participate in a complex network of interdependent interactions that define the position and functional organization of adherens junctions and tight junctions. However, the biochemical pathways through which they control polarity are poorly understood. In this study, we identify an interaction between endogenous hDlg1 and MPP7, a previously uncharacterized MAGUK-p55 subfamily member. We find that MPP7 targets to the lateral surface of epithelial cells via its L27N domain, through an interaction with hDlg1. Loss of either hDlg1 or MPP7 from epithelial Caco-2 cells results in a significant defect in the assembly and maintenance of functional tight junctions. We conclude that the formation of a complex between hDlg1 and MPP7 promotes epithelial cell polarity and tight junction formation.


This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-11-0980) on March 1, 2007.

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

{ddagger} Present address: Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 572, New York, NY 10021.

Address correspondence to: Alan Hall (halla{at}mskcc.org)

Abbreviations used: PDZ, PSD-95, ZO-1, and Discs-large; MPP, membrane-palmitoylated protein.




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