title: Crumbs3 is essential for proper epithelial development and viability.
abstract: First identified in Drosophila, the Crumbs (Crb) proteins are important in epithelial polarity, apical membrane formation, and tight junction (TJ) assembly. The conserved Crb intracellular region includes a FERM (band 4.1/ezrin/radixin/moesin) binding domain (FBD) whose mammalian binding partners are not well understood and a PDZ binding motif that interacts with mammalian Pals1 (protein associated with lin seven) (also known as MPP5). Pals1 binds Patj (Pals1-associated tight-junction protein), a multi-PDZ-domain protein that associates with many tight junction proteins. The Crb complex also binds the conserved Par3/Par6/atypical protein kinase C (aPKC) polarity cassette that restricts migration of basolateral proteins through phosphorylation. Here, we describe a Crb3 knockout mouse that demonstrates extensive defects in epithelial morphogenesis. The mice die shortly after birth, with cystic kidneys and proteinaceous debris throughout the lungs. The intestines display villus fusion, apical membrane blebs, and disrupted microvilli. These intestinal defects phenocopy those of Ezrin knockout mice, and we demonstrate an interaction between Crumbs3 and ezrin. Taken together, our data indicate that Crumbs3 is crucial for epithelial morphogenesis and plays a role in linking the apical membrane to the underlying ezrin-containing cytoskeleton.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Eileen L
authors.initials: EL
authors.lastname: Whiteman
authors.forename: Shuling
authors.initials: S
authors.lastname: Fan
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Harder
authors.forename: Katherine D
authors.initials: KD
authors.lastname: Walton
authors.forename: Chia-Jen
authors.initials: CJ
authors.lastname: Liu
authors.forename: Abdul
authors.initials: A
authors.lastname: Soofi
authors.forename: Vanessa C
authors.initials: VC
authors.lastname: Fogg
authors.forename: Marc B
authors.initials: MB
authors.lastname: Hershenson
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Dressler
authors.forename: Gail H
authors.initials: GH
authors.lastname: Deutsch
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Gumucio
authors.forename: Ben
authors.initials: B
authors.lastname: Margolis
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D016764:Cell Polarity; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000648:ultrastructure; D004848:Epithelium / Q000196:embryology / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D007668:Kidney / Q000196:embryology / Q000378:metabolism*; D008168:Lung / Q000196:embryology / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D016019:Survival Analysis; D019108:Tight Junctions / Q000378:metabolism; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D000099149:Ezrin; C530695:Crb3 protein, mouse