CRB3 binds directly to Par6 and regulates the morphogenesis of the tight junctions in mammalian epithelial cells.
Crumbs is an apical transmembrane protein crucial for epithelial morphogenesis in Drosophila melanogaster embryos. A protein with all the characteristics for a Crumbs homologue has been identified from patients suffering from retinitis pigmentosa group 12, but this protein (CRB1) is only expressed in retina and some parts of the brain, both in human and mouse. Here, we describe CRB3, another Crumbs homologue that is preferentially expressed in epithelial tissues and skeletal muscles in human. CRB3 shares the conserved cytoplasmic domain with other Crumbs but exhibits a very short extracellular domain without the EGF- and laminin A-like G repeats present in the other Crumbs. CRB3 is localized to the apical and subapical area of epithelial cells from the mouse and human intestine, suggesting that it could play a role in epithelial morphogenesis. Indeed, expression of CRB3 or of a chimera containing the extracellular domain of the neurotrophin receptor p75NTR and the transmembrane and cytoplasmic domains of CRB3 led to a slower development of functional tight junctions in Madin-Darby canine kidney cells. This phenotype relied on the presence of CRB3 four last amino acids (ERLI) that are involved in a direct interaction with Par6, a regulator of epithelial polarity and tight junction formation. Thus, CRB3, through its cytoplasmic domain and its interactors, plays a role in apical membrane morphogenesis and tight junction regulation.
Lemmers
Céline
C
Laboratoire de Neurogenèse et Morphogenèse au cours du Développement et chez l'Adulte, Unité Mixte Recherche 6156 Centre National de la Recherche Scientifique, Université de la Méditerranée, Marseille, France.
Michel
Didier
D
Lane-Guermonprez
Lydie
L
Delgrossi
Marie-Hélène
MH
Médina
Emmanuelle
E
Arsanto
Jean-Pierre
JP
Le Bivic
André
A
D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D016764:Cell Polarity / Q000502:physiology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D016253:Microscopy, Immunoelectron; D009024:Morphogenesis; D011485:Protein Binding; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism* / Q000648:ultrastructure; D020798:Two-Hybrid System Techniques
C472002:CRB3 protein, human; D008562:Membrane Glycoproteins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor