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

VIB Department of Medical Protein Research, Ghent University, Gand, Flanders, Belgium
Molecular Biology of the Cell (Impact Factor: 4.47). 06/2007; 18(5):1744-55. DOI: 10.1091/mbc.E06-11-0980
Source: PubMed


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.

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    • "Second, Dlg1 associates through its L27N domain with a number of related MAGUK family proteins, including Lin2/ CASK, MPP2, MPP3, and MPP7 (Bohl et al., 2007). MPP7 colocalizes with Dlg1 to the lateral membrane, and gene silencing of either MPP7 or Dlg1 delays the formation of functional tight junctions, suggesting that they function together in this context (Stucke et al., 2007). By contrast, CASK colocalizes with Dlg1 along the basal membrane, indicating that the interactions between other MAGUK proteins and Dlg1 might be mutually exclusive. "
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    • "MAGUK proteins are found at areas of cell-cell contact, where they are essential for multi-protein complex assembly. MPP7 forms a tripartite complex with Discs Large 1(DLG1) and Lin7, and is necessary for maintenance of cell polarity [32,33]. Interestingly, HNF4A, the gene responsible for MODY1, has also been shown to be important in formation of tight junctions [34]. "
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