Neuralized regulates Crumbs endocytosis and epithelium morphogenesis via specific Stardust isoforms

Gantas Perez-Mockus (1, 2) , Vanessa Roca (1) , Khalil Mazouni (1) , François Schweisguth (1)

1 Cellules Souches et Développement / Stem Cells and Development
2 Cellule Pasteur UPMC

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.

Domains: Development Biology

Gantas Perez-Mockus, Vanessa Roca, Khalil Mazouni, François Schweisguth. Neuralized regulates Crumbs endocytosis and epithelium morphogenesis via specific Stardust isoforms. Journal of Cell Biology, 2017, 216 (5), pp.1405 - 1420. ⟨10.1083/jcb.201611196⟩. ⟨pasteur-01799354⟩