title: Mammalian Crumbs3 is a small transmembrane protein linked to protein associated with Lin-7 (Pals1).
abstract: Drosophila Crumbs is a transmembrane protein that plays an important role in epithelial cell polarity and photoreceptor development. Overexpression of Crumbs in Drosophila epithelia expands the apical surface and leads to disruption of cell polarity. Drosophila Crumbs also interacts with two other polarity genes, Stardust and Discs Lost. Recent work has identified a human orthologue of Drosophila Crumbs, known as CRB1, that is mutated in the eye disorders, retinitis pigmentosa and Leber congenital amaurosis. Our work has demonstrated that human CRB1 can form a complex with mammalian orthologues of Stardust and Discs Lost, known as protein associated with Lin-7 (Pals1) and Pals1 associated tight junction (PATJ), respectively. In the current report we have cloned a full length cDNA for a human paralogue of CRB1 called Crumbs3 (CRB3). In contrast to Drosophila Crumbs and CRB1, CRB3 has a very short extracellular domain but like these proteins it has a conserved intracellular domain that allows it to complex with Pals1 and PATJ. Mouse and human CRB3 have identical intracellular domains but divergent extracellular domains except for a conserved N-glycosylation site. CRB3 is localized to the apical surface and tight junctions but the conserved N linked glycosylation site does not appear to be necessary for CRB3 apical targeting. CRB3 is a specialized isoform of the Crumbs protein family that is expressed in epithelia and can tie the apical membrane to the tight junction.
authors.affiliation: Howard Hughes Medical Institute, University of Michigan Medical School, 4570 MSRB II, Box 0650, 1150 W. Medical Center Drive, Ann Arbor, MI 48109-0650, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Makarova
authors.forename: Michael H
authors.initials: MH
authors.lastname: Roh
authors.forename: Chia-Jen
authors.initials: CJ
authors.lastname: Liu
authors.forename: Stephanie
authors.initials: S
authors.lastname: Laurinec
authors.forename: Ben
authors.initials: B
authors.lastname: Margolis
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D011485:Protein Binding; D051381:Rats; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D033921:Vesicular Transport Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C472002:CRB3 protein, human; D018076:DNA, Complementary; C119588:LIN-7 protein, mammalian; C486532:LIN7A protein, human; C486531:LIN7C protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins