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 |
10.092
|
Times Cited |
34
|
WOS Category
|
DEVELOPMENTAL BIOLOGY
CELL BIOLOGY
|
Resource |
Medaka |
ojoplano (MT934) |