Letter abstract
Nature Cell Biology 5, 137 - 142 (2003)
Published online: 27 January 2003 | doi:10.1038/ncb923
Direct interaction of two polarity complexes implicated in epithelial tight junction assembly
Toby W. Hurd1,5, Lin Gao4,5, Michael H. Roh2, Ian G. Macara4 & Ben Margolis1,2,3
Tight junctions help establish polarity in mammalian epithelia by forming a physical barrier that separates apical and basolateral membranes. Two evolutionarily conserved multi-protein complexes, Crumbs (Crb)–PALS1 (Stardust)–PATJ (DiscsLost)1, 2, 3, 4 and Cdc42–Par6–Par3–atypical protein kinase C (aPKC), have been implicated in the assembly of tight junctions and in polarization of Drosophila melanogaster epithelia5, 6, 7, 8. Here we identify a biochemical and functional link between these two complexes that is mediated by Par6 and PALS1 (proteins associated with Lin7). The interaction between Par6 and PALS1 is direct, requires the amino terminus of PALS1 and the PDZ domain of Par6, and is regulated by Cdc42-GTP. The transmembrane protein Crb can recruit wild-type Par6, but not Par6 with a mutated PDZ domain, to the cell surface. Expression of dominant-negative PALS1-associated tight junction protein (PATJ) in MDCK cells results in mis-localization of PALS1, members of the Par3–Par6–aPKC complex and the tight junction marker, ZO-1. Similarly, overexpression of Par6 in MDCK cells inhibits localization of PALS1 to the tight junction. Our data highlight a previously unrecognized link between protein complexes that are essential for epithelial polarity and formation of tight junctions.
- Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI 48109-0650, USA
- Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109-0650, USA
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0650, USA
- Center for Cell Signalling, University of Virginia Health Sciences Center, Charlottesville, VA 22908-0577, USA
- These authors contributed equally to this work
Correspondence to: Ian G. Macara4 e-mail: imacara@virginia.edu
Correspondence to: Ben Margolis1,2,3 e-mail: bmargoli@umich.edu
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