Numb/Numbl-Opo Antagonism Controls Retinal Epithelium Morphogenesis by Regulating Integrin Endocytosis

Dev Cell. 2012 Oct 16;23(4):782-95. doi: 10.1016/j.devcel.2012.09.004. Epub 2012 Oct 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • Fish Proteins
  • Integrins
  • Membrane Proteins
  • Nerve Tissue Proteins