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 (PAT) 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.
机构:Univ Calif San Francisco, Program Cell Biol Cellular & Mol Pharmacol & Psyc, San Francisco, CA 94143 USA
Cao, TT
;
Deacon, HW
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Program Cell Biol Cellular & Mol Pharmacol & Psyc, San Francisco, CA 94143 USA
Deacon, HW
;
Reczek, D
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Program Cell Biol Cellular & Mol Pharmacol & Psyc, San Francisco, CA 94143 USA
Reczek, D
;
Bretscher, A
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Program Cell Biol Cellular & Mol Pharmacol & Psyc, San Francisco, CA 94143 USA
Bretscher, A
;
von Zastrow, M
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Program Cell Biol Cellular & Mol Pharmacol & Psyc, San Francisco, CA 94143 USAUniv Calif San Francisco, Program Cell Biol Cellular & Mol Pharmacol & Psyc, San Francisco, CA 94143 USA
机构:Univ Calif San Francisco, Program Cell Biol Cellular & Mol Pharmacol & Psyc, San Francisco, CA 94143 USA
Cao, TT
;
Deacon, HW
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Program Cell Biol Cellular & Mol Pharmacol & Psyc, San Francisco, CA 94143 USA
Deacon, HW
;
Reczek, D
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Program Cell Biol Cellular & Mol Pharmacol & Psyc, San Francisco, CA 94143 USA
Reczek, D
;
Bretscher, A
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Program Cell Biol Cellular & Mol Pharmacol & Psyc, San Francisco, CA 94143 USA
Bretscher, A
;
von Zastrow, M
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Program Cell Biol Cellular & Mol Pharmacol & Psyc, San Francisco, CA 94143 USAUniv Calif San Francisco, Program Cell Biol Cellular & Mol Pharmacol & Psyc, San Francisco, CA 94143 USA