hINADl/PATJ, a homolog of discs lost, interacts with crumbs and localizes to tight junctions in human epithelial cells.
dCrumbs is an apical organizer crucial for the maintenance of epithelial polarity in Drosophila (1). It is known that dCrumbs interacts with Discs lost (Dlt), a protein with four PDZ (PSD95/Discs Large/ZO-1) domains (2), and Stardust (Sdt), a protein of the MAGUK (membrane-associated guanylate kinase) family (3, 4). We have searched for potential homologs of Dlt in human epithelial cells and characterized one of them in intestinal epithelial cells. Human INAD-like (hINADl) contains 8 PDZ domains, is concentrated in tight junctions, and is also found at the apical plasma membrane. Overexpression of hINADl disrupted the tight junctions localization of ZO-1 and 3. We also identified a partial cDNA coding the transmembrane and cytoplasmic domains of a new human crumbs (CRB3) expressed in Caco-2 cells. This CRB3 was able to interact through its C-terminal end with the N-terminal domain of hINADl. Taken together, the data indicate that hINADl is likely to represent a Dlt homolog in mammalian epithelial cells and might be involved in regulating the integrity of tight junctions. We thus propose to rename hINADl PATJ for protein associated to tight junctions.
Lemmers
Céline
C
Laboratoire de Neurogenèse et Morphogenèse du Développement à l'Adulte (NMDA, Unité Mixte de Recherche 6165), Institut de Biologie du Développement de Marseille, Faculté des Sciences de Luminy, Université de la Méditerranée, France.
Médina
Emmanuelle
E
Delgrossi
Marie-Hélène
MH
Michel
Didier
D
Arsanto
Jean-Pierre
JP
Le Bivic
André
A
D000595:Amino Acid Sequence; D001483:Base Sequence; D018938:Caco-2 Cells; D017931:DNA Primers; D029721:Drosophila Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005136:Eye Proteins; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D062725:Tight Junction Proteins; D019108:Tight Junctions / Q000378:metabolism*
D017931:DNA Primers; D029721:Drosophila Proteins; D005136:Eye Proteins; D008565:Membrane Proteins; C107903:PATJ protein, human; D062725:Tight Junction Proteins; C064360:crb protein, Drosophila