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Vol. 15, Issue 3, 1324-1333, March 2004
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Laboratoire de Neurogenèse et Morphogenèse au cours du Développement et chez l'Adulte, Unité Mixte Recherche 6156 Centre National de la Recherche Scientifique, Institut de Biologie du Développment de Marseille, Université de la Méditerranée, Campus de Luminy, 13288 Marseille, France
Submitted April 16, 2003;
Revised September 26, 2003;
Accepted October 24, 2003
Monitoring Editor: Mark Ginsberg
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.
Abbreviations used: MDCK, Madin-Darby kidney cell; NTR, neurotrophin receptor; PATJ, protein associated to tight junctions; PDZ, PSD95/Discs large/ZO-1; PRC, photoreceptor cell; TJ, tight junction.
* These authors contributed equally to this work.
Corresponding author. E-mail address: lebivic{at}ibdm.univ-mrs.fr.
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