title: Neuralized regulates Crumbs endocytosis and epithelium morphogenesis via specific Stardust isoforms.
abstract: Crumbs (Crb) is a conserved determinant of apical membrane identity that regulates epithelial morphogenesis in many developmental contexts. In this study, we identify the Crb complex protein Stardust (Sdt) as a target of the E3 ubiquitin ligase Neuralized (Neur) inDrosophila melanogasterNeur interacts with and down-regulates specific Sdt isoforms containing a Neur binding motif (NBM). Using a CRISPR (clustered regularly interspaced short palindromic repeats)-induced deletion of the NBM-encoding exon, we found that Sdt is a key Neur target and that Neur acts via Sdt to down-regulate Crb. We further show that Neur promotes the endocytosis of Crb via the NBM-containing isoforms of Sdt. Although the regulation of Crb by Neur is not strictly essential, it contributes to epithelium remodeling in the posterior midgut and thereby facilitates the trans-epithelial migration of the primordial germ cells in early embryos. Thus, our study uncovers a novel regulatory mechanism for the developmental control of Crb-mediated morphogenesis.
authors.affiliation: Department of Developmental and Stem Cell Biology, Institut Pasteur, F-75015 Paris, France.|Centre National de la Recherché Scientifique, UMR3738, F-75015 Paris, France.|Cellule Pasteur, Université Pierre et Marie Curie, F-75015 Paris, France.
authors.forename: Gantas
authors.identifier: 0000-0002-9287-2310
authors.initials: G
authors.lastname: Perez-Mockus
authors.affiliation: Department of Developmental and Stem Cell Biology, Institut Pasteur, F-75015 Paris, France.|Centre National de la Recherché Scientifique, UMR3738, F-75015 Paris, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Roca
authors.affiliation: Department of Developmental and Stem Cell Biology, Institut Pasteur, F-75015 Paris, France.|Centre National de la Recherché Scientifique, UMR3738, F-75015 Paris, France.
authors.forename: Khalil
authors.initials: K
authors.lastname: Mazouni
authors.affiliation: Department of Developmental and Stem Cell Biology, Institut Pasteur, F-75015 Paris, France fschweis@pasteur.fr.|Centre National de la Recherché Scientifique, UMR3738, F-75015 Paris, France.
authors.forename: François
authors.identifier: 0000-0001-8888-9390
authors.initials: F
authors.lastname: Schweisguth
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D004705:Endocytosis; D004848:Epithelium / Q000378:metabolism*; D051528:Guanylate Kinases / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009024:Morphogenesis; D020033:Protein Isoforms / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D020033:Protein Isoforms; C064360:crb protein, Drosophila; D051528:Guanylate Kinases; C444479:sdt protein, Drosophila