[Atp6ap2/ (Pro) renin Receptor is Required for Laminar Formation during Retinal Development in Mice]

Nippon Ganka Gakkai Zasshi. 2015 Nov;119(11):787-98.
[Article in Japanese]

Abstract

(Pro) renin receptor [(P) RR], a key molecule for tissue renin-angiotensin system, was originally identified as Atp6ap2, an accessory subunit for vacuolar H(+)-ATPase that is a multi-subunit proton pump involved in fundamental cellular physiology. In this study, to elucidate the physiological functions of Atp6ap2/ (P) RR during retinal development in mammals, we used Cre-LoxP system to generate photoreceptor-specific conditional knock-out (CKO) mice, and revealed a critical role of Atp6ap2/(P) RR in photoreceptor development. Deletion of photoreceptor Atp6ap2/ (P) RR did not affect retinal cell differentiation, but led to laminar disorganization in the photoreceptor layer with dysfunction of photoreceptors. Cell adhesion and polarity molecules, all of which were co-localized with Atp6ap2 at the apical edge of the developing retina, were dispersed together with mislocalization of retinal progenitors apart from the apical surface in Atp6ap2 conditional knockout mice. Among these molecules, co-immunoprecipitation using retinal homogenates and Atp6ap2/(P) RR-transfected cells showed that Atp6ap2/(P) RR interacted with partitioning defective 3 homolog (Par3) protein, known to play a pivotal role in planar cell polarity in the Par-atypical protein kinase C system. Atp6ap2 interacted with Par3 protein that plays a pivotal role in planar cell polarity. Our data provide a novel function of Atp6ap2 required as a cell polarity determinant for retinal laminar formation.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Cell Adhesion
  • Cell Adhesion Molecules / metabolism
  • Cell Cycle Proteins
  • Cell Differentiation
  • Humans
  • Mice
  • Protein Binding
  • Proton-Translocating ATPases / genetics
  • Proton-Translocating ATPases / metabolism*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Retina / cytology
  • Retina / embryology
  • Retina / growth & development*
  • Retina / metabolism*

Substances

  • ATP6AP2 protein, mouse
  • Adaptor Proteins, Signal Transducing
  • Cell Adhesion Molecules
  • Cell Cycle Proteins
  • Pard3 protein, mouse
  • Receptors, Cell Surface
  • Proton-Translocating ATPases