title: Numb/Numbl-Opo antagonism controls retinal epithelium morphogenesis by regulating integrin endocytosis.
abstract: Polarized trafficking of adhesion receptors plays a pivotal role in controlling cellular behavior during morphogenesis. Particularly, clathrin-dependent endocytosis of integrins has long been acknowledged as essential for cell migration. However, little is known about the contribution of integrin trafficking to epithelial tissue morphogenesis. Here we show how the transmembrane protein Opo, previously described for its essential role during optic cup folding, plays a fundamental role in this process. Through interaction with the PTB domain of the clathrin adaptors Numb and Numbl via an integrin-like NPxF motif, Opo antagonizes Numb/Numbl function and acts as a negative regulator of integrin endocytosis in vivo. Accordingly, numb/numbl gain-of-function experiments in teleost embryos mimic the retinal malformations observed in opo mutants. We propose that developmental regulator Opo enables polarized integrin localization by modulating Numb/Numbl, thus directing the basal constriction that shapes the vertebrate retina epithelium.
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CSIC/UPO/JA), 41013 Sevilla, Spain.
authors.forename: Ozren
authors.initials: O
authors.lastname: Bogdanović
authors.forename: Mariana
authors.initials: M
authors.lastname: Delfino-Machín
authors.forename: María
authors.initials: M
authors.lastname: Nicolás-Pérez
authors.forename: María P
authors.initials: MP
authors.lastname: Gavilán
authors.forename: Inês
authors.initials: I
authors.lastname: Gago-Rodrigues
authors.forename: Ana
authors.initials: A
authors.lastname: Fernández-Miñán
authors.forename: Concepción
authors.initials: C
authors.lastname: Lillo
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Ríos
authors.forename: Joachim
authors.initials: J
authors.lastname: Wittbrodt
authors.forename: Juan R
authors.initials: JR
authors.lastname: Martínez-Morales
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004705:Endocytosis; D029941:Fish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009990:Oryzias; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*
chemical_list: D029941:Fish Proteins; D016023:Integrins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins