RRC ID 30225
Author Bogdanović O, Delfino-Machín M, Nicolás-Pérez M, Gavilán MP, Gago-Rodrigues I, Fernández-Miñán A, Lillo C, Ríos RM, Wittbrodt J, Martínez-Morales JR.
Title Numb/Numbl-Opo antagonism controls retinal epithelium morphogenesis by regulating integrin endocytosis.
Journal Dev Cell
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.
Volume 23(4)
Pages 782-95
Published 2012-10-16
DOI 10.1016/j.devcel.2012.09.004
PII S1534-5807(12)00415-7
PMID 23041384
MeSH Animals Cells, Cultured Endocytosis* Fish Proteins / antagonists & inhibitors Fish Proteins / genetics Fish Proteins / metabolism HeLa Cells Humans Integrins / metabolism* Membrane Proteins / genetics Membrane Proteins / metabolism* Nerve Tissue Proteins / antagonists & inhibitors* Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism Oryzias Retinal Pigment Epithelium / cytology Retinal Pigment Epithelium / embryology* Retinal Pigment Epithelium / metabolism*
IF 9.19
Times Cited 34
Medaka ojoplano (MT934)