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Published 1 April 2002. doi:10.1083/jcb.200109010
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© The Rockefeller University Press, 0021-9525/2002/4/161 $5.00
The Journal of Cell Biology, Volume 157, Number 1, April 1, 2002 161-172

Article

The Maguk protein, Pals1, functions as an adapter, linking mammalian homologues of Crumbs and Discs Lost



Michael H. Roh1, Olga Makarova2, Chia-Jen Liu, KunYoo3, Shin1, Seonok Lee1, Stephanie Laurinec2, Meera Goyal3, Roger Wiggins3 and Ben Margolis1,2,3

1 Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109
2 Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI 48109
3 Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109

Address correspondence to Ben Margolis, Howard Hughes Medical Institute, University of Michigan Medical Center, 4570 MSRB II, Box 0650, 1150 W. Medical Center Dr., Ann Arbor, MI 48109-0650. Tel.: (734) 764-3567. Fax: (734) 763-9323. E-mail: bmargoli{at}umich.edu

Membrane-associated guanylate kinase (Maguk) proteins are scaffold proteins that contain PSD-95–Discs Large–zona occludens-1 (PDZ), Src homology 3, and guanylate kinase domains. A subset of Maguk proteins, such as mLin-2 and protein associated with Lin-7 (Pals)1, also contain two L27 domains: an L27C domain that binds mLin-7 and an L27N domain of unknown function. Here, we demonstrate that the L27N domain targets Pals1 to tight junctions by binding to a PDZ domain protein, Pals1-associated tight junction (PATJ) protein, via a unique Maguk recruitment domain. PATJ is a homologue of Drosophila Discs Lost, a protein that is crucial for epithelial polarity and that exists in a complex with the apical polarity determinant, Crumbs. PATJ and a human Crumbs homologue, CRB1, colocalize with Pals1 to tight junctions, and CRB1 interacts with PATJ albeit indirectly via binding the Pals1 PDZ domain. In agreement, we find that a Drosophila homologue of Pals1 participates in identical interactions with Drosophila Crumbs and Discs Lost. This Drosophila Pals1 homologue has been demonstrated recently to represent Stardust, a crucial polarity gene in Drosophila. Thus, our data identifies a new multiprotein complex that appears to be evolutionarily conserved and likely plays an important role in protein targeting and cell polarity.

Key Words: Maguk; PDZ domain; Discs Lost; Stardust; Crumbs


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