The MAGUK protein MPP7 binds to the polarity protein hDlg1 and facilitates epithelial tight junction formation.
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.
Stucke
Volker M
VM
Medical Research Council Laboratory for Molecular Cell Biology, Cancer Research UK Oncogene and Signal Transduction Group, University College London, London WC1E 6BT, England.
Timmerman
Evy
E
Vandekerckhove
Joel
J
Gevaert
Kris
K
Hall
Alan
A
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D018938:Caco-2 Cells; D002460:Cell Line; D016764:Cell Polarity; D018076:DNA, Complementary / Q000235:genetics; D000074288:Discs Large Homolog 1 Protein; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism*; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; C472002:CRB3 protein, human; C513314:DLG1 protein, human; D018076:DNA, Complementary; D000074288:Discs Large Homolog 1 Protein; C482290:MPP7 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011994:Recombinant Proteins