PATJ connects and stabilizes apical and lateral components of tight junctions in human intestinal cells.
The Crumbs complex that also contains the cortical proteins Stardust and DPATJ (a homologue of PATJ), is crucial for the building of epithelial monolayers in Drosophila. Although loss of function of the Crumbs or Stardust genes prevents the stabilization of a belt of adherens junctions at the apico-lateral border of the cells, no phenotype has been described for the Dpatj gene and its role in epithelial morphogenesis and polarity remains unknown. We have produced downregulated PATJ stable lines of Caco2 to clarify its role in epithelial morphogenesis. In PATJ knockdown cells, Pals1 (a Stardust homologue) is no longer associated with tight junctions whereas Crumbs3 (Crb3) is accumulated into a compartment spatially close to the apical membrane and related to early endosomes. Furthermore, occludin and ZO-3, two proteins of tight junctions are mislocalized on the lateral membrane indicating that PATJ plays a novel role in the building of tight junctions by providing a link between their lateral and apical components. Thus, PATJ stabilizes the Crb3 complex and regulates the spatial concentration of several components at the border between the apical and lateral domains.
Michel
Didier
D
UMR 6156, NMDA, Institute of Developmental Biology of Marseille, Faculté des Sciences de Luminy, case 907, 13288 Marseille Cedex 09, France.
Arsanto
Jean-Pierre
JP
Massey-Harroche
Dominique
D
Béclin
Christophe
C
Wijnholds
Jan
J
Le Bivic
André
A
D000818:Animals; D018938:Caco-2 Cells / Q000378:metabolism* / Q000648:ultrastructure; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D004330:Drosophila / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism; D062793:Occludin; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D062725:Tight Junction Proteins; D019108:Tight Junctions / Q000378:metabolism* / Q000648:ultrastructure; D062825:Zonula Occludens Proteins
D002352:Carrier Proteins; D005136:Eye Proteins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; C107903:PATJ protein, human; D034741:RNA, Small Interfering; C111873:TJP3 protein, human; D062725:Tight Junction Proteins; D062825:Zonula Occludens Proteins; D009703:Nucleoside-Phosphate Kinase; C501307:MPP5 protein, human