title: Dlg5 maintains apical polarity by promoting membrane localization of Crumbs during Drosophila oogenesis.
abstract: Apical-basal polarity plays critical roles in the functions of epithelial tissues. However, the mechanisms of epithelial polarity establishment and maintenance remain to be fully elucidated. Here we show that the membrane-associated guanylate kinase (MAGUK) family protein Dlg5 is required for the maintenance of apical polarity of follicle epithelium during Drosophila oogenesis. Dlg5 localizes at the apical membrane and adherens junction (AJ) of follicle epithelium in early stage egg chambers. Specifically, we demonstrate that the major function of Dlg5 is to promote apical membrane localization of Crumbs, since overexpression of Crumbs but not other major apical or AJ components could rescue epithelial polarity defects resulted from loss of Dlg5. Furthermore, we performed a structure-function analysis of Dlg5 and found that the C-terminal PDZ3 and PDZ4 domains are required for all Dlg5's functions as well as its ability to localize to apical membrane. The N-terminal coiled-coil motif could be individually targeted to the apical membrane, while the central linker region could be targeted to AJ. Lastly, the MAGUK core domains of PDZ4-SH3-GUK could be individually targeted to apical, AJ and basolateral membranes.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Nanjing University, 12 Xue-fu Road, Nanjing, China 210061.
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Nanjing University, 12 Xue-fu Road, Nanjing, China 210061.
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Nanjing University, 12 Xue-fu Road, Nanjing, China 210061.
authors.forename: Di
authors.initials: D
authors.lastname: Kang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Nanjing University, 12 Xue-fu Road, Nanjing, China 210061.
authors.forename: Xuan
authors.initials: X
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Nanjing University, 12 Xue-fu Road, Nanjing, China 210061.
authors.forename: Ping
authors.initials: P
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Nanjing University, 12 Xue-fu Road, Nanjing, China 210061.
authors.forename: Dou
authors.initials: D
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center, Nanjing University, 12 Xue-fu Road, Nanjing, China 210061.
authors.forename: Jiong
authors.initials: J
authors.lastname: Chen
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity; D004330:Drosophila / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D051528:Guanylate Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009154:Mutation; D009866:Oogenesis; D006080:Ovarian Follicle / Q000378:metabolism; D054731:PDZ Domains
chemical_list: C000627073:Dlg5 protein, Drosophila; D029721:Drosophila Proteins; D008565:Membrane Proteins; C064360:crb protein, Drosophila; D051528:Guanylate Kinases