The Maguk protein, Pals1, functions as an adapter, linking mammalian homologues of Crumbs and Discs Lost.
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.
Roh
Michael H
MH
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Makarova
Olga
O
Liu
Chia-Jen
CJ
Shin
KunYoo
K
Lee
Seonok
S
Laurinec
Stephanie
S
Goyal
Meera
M
Wiggins
Roger
R
Margolis
Ben
B
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D017124:Conserved Sequence; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D051528:Guanylate Kinases; D006801:Humans; D019476:Insect Proteins / Q000235:genetics; D007668:Kidney / Q000166:cytology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D009419:Nerve Tissue Proteins; D009703:Nucleoside-Phosphate Kinase / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D062725:Tight Junction Proteins; D019108:Tight Junctions / Q000378:metabolism*; D033921:Vesicular Transport Proteins
D048868:Adaptor Proteins, Signal Transducing; C448939:CRB1 protein, human; D002352:Carrier Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D019476:Insect Proteins; C119588:LIN-7 protein, mammalian; C486532:LIN7A protein, human; C486531:LIN7C protein, human; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C107903:PATJ protein, human; C575001:Patj protein, rat; D062725:Tight Junction Proteins; D033921:Vesicular Transport Proteins; C064360:crb protein, Drosophila; C118488:dlt protein, Drosophila; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases; C444479:sdt protein, Drosophila