The Maguk protein, Pals1, functions as an adapter, linking mammalian homologues of crumbs and discs lost

Michael H. Roh, Olga Makarova, Chia Jen Liu, Kunyoo Shin, Seonok Lee, Stephanie Laurinec, Meera Goyal, Roger Wiggins, Ben Margolis

Research output: Contribution to journalArticle

266 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)161-172
Number of pages12
JournalJournal of Cell Biology
Volume157
Issue number1
DOIs
StatePublished - Apr 1 2002

Keywords

  • Crumbs
  • Discs Lost
  • Maguk
  • PDZ domain
  • Stardust

ASJC Scopus subject areas

  • Cell Biology

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    Roh, M. H., Makarova, O., Liu, C. J., Shin, K., Lee, S., Laurinec, S., Goyal, M., Wiggins, R., & Margolis, B. (2002). The Maguk protein, Pals1, functions as an adapter, linking mammalian homologues of crumbs and discs lost. Journal of Cell Biology, 157(1), 161-172. https://doi.org/10.1083/jcb.200109010