Neuralized regulates Crumbs endocytosis and epithelium morphogenesis via specific Stardust isoforms
| Autor: | Khalil Mazouni, François Schweisguth, Vanessa Roca, Gantas Perez-Mockus |
|---|---|
| Přispěvatelé: | Cellules Souches et Développement / Stem Cells and Development, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Cellule Pasteur UPMC, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris], This work was funded by an Agence Nationale de la Recherche grant (ANR12-BSV2-0010-01). G. Perez-Mockus received fellowships from the Ministére de l’Education Nationale de la Recherche et de la Technologie and the Fondation pour la Recherche Médicale., ANR-12-BSV2-0010,ShaPiShaPo,Mécanismes de régulation de la morphogenèse épitheliale chez la drosophile : étude de l'ubiquitine ligase E3 Neuralized(2012), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Gene isoform animal structures Morphogenesis Endocytosis Article Epithelium MESH: Drosophila melanogaster 03 medical and health sciences Exon MESH: Guanylate Kinases/metabolism Animals Drosophila Proteins Protein Isoforms CRISPR MESH: Membrane Proteins/metabolism MESH: Animals [SDV.BDD]Life Sciences [q-bio]/Development Biology Research Articles MESH: Drosophila Proteins/metabolism Genetics MESH: Epithelium/metabolism biology Membrane Proteins Membrane Transport Proteins Cell Biology Apical membrane biology.organism_classification MESH: Morphogenesis Ubiquitin ligase Cell biology Drosophila melanogaster 030104 developmental biology MESH: Endocytosis biology.protein MESH: Membrane Transport Proteins/metabolism Guanylate Kinases MESH: Protein Isoforms/metabolism |
| Zdroj: | Journal of Cell Biology Journal of Cell Biology, Rockefeller University Press, 2017, 216 (5), pp.1405-1420. ⟨10.1083/jcb.201611196⟩ The Journal of Cell Biology Journal of Cell Biology, 2017, 216 (5), pp.1405-1420. ⟨10.1083/jcb.201611196⟩ |
| ISSN: | 0021-9525 1540-8140 |
| DOI: | 10.1083/jcb.201611196⟩ |
| Popis: | The E3 ubiquitin ligase Neuralized is shown to interact with a subset of the Stardust isoforms to regulate the endocytosis of the apical protein Crumbs and thereby promote epithelial remodeling during Drosophila development. 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) in Drosophila melanogaster. Neur 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. |
| Databáze: | OpenAIRE |
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