Atp6ap2/(Pro)renin receptor interacts with Par3 as a cell polarity determinant required for laminar formation during retinal development in mice

Atsuhiro Kanda, Kousuke Noda, Kenya Yuki, Yoko Ozawa, Takahisa Furukawa, Atsuhiro Ichihara, Susumu Ishida

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

(Pro)renin receptor [(P)RR], also known as Atp6ap2, has attracted growing attention as a key molecule for tissue renin-angiotensin system (RAS). In addition to its role in tissueRASactivation, Atp6ap2/(P)RR was originally identified as an accessory subunit for vacuolar H+-ATPase (v-ATPase), which is a multisubunit proton pump involved in diverse and fundamental cellular physiology. In this study, to elucidate the physiological function 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 around the outer nuclear layer together with severe dysfunction of photoreceptor cells. In the CKO mice, cell adhesion and polarity molecules, some of which were colocalized with Atp6ap2/(P)RR at the apical edge of the wild-type developing retina, were substantially dispersed together with mislocalization of retinal progenitor cells apart from the apical surface. Among theses molecules, coimmunoprecipitation using retinal homogenates and ATP6AP2/(P)RR-transfected cells showed that Atp6ap2/(P)RR interacted with partitioning defective 3 homolog (PAR3) protein, which is known to function in the Par-atypical protein kinase C (aPKC) system. Furthermore, yeast two-hybrid assays demonstrated direct molecular interaction between ATP6AP2/(P)RR and PAR3. Our present data revealed the novel function of Atp6ap2/ (P)RR required for laminar formation during retinal development. We propose that this cellular activity associated with the Par-aPKC system, in addition to the v-ATPase function and tissue RAS activation, is the third biological role of Atp6ap2/(P)RR.

Original languageEnglish
Pages (from-to)19341-19351
Number of pages11
JournalJournal of Neuroscience
Volume33
Issue number49
DOIs
Publication statusPublished - 2013

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Vacuolar Proton-Translocating ATPases
Cell Polarity
Renin-Angiotensin System
Renin
Knockout Mice
Proton Pumps
Photoreceptor Cells
Two-Hybrid System Techniques
Cell Adhesion Molecules
Retina
Cell Differentiation
Mammals
Stem Cells
Proteins
PKC-3 protein

ASJC Scopus subject areas

  • Neuroscience(all)

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Atp6ap2/(Pro)renin receptor interacts with Par3 as a cell polarity determinant required for laminar formation during retinal development in mice. / Kanda, Atsuhiro; Noda, Kousuke; Yuki, Kenya; Ozawa, Yoko; Furukawa, Takahisa; Ichihara, Atsuhiro; Ishida, Susumu.

In: Journal of Neuroscience, Vol. 33, No. 49, 2013, p. 19341-19351.

Research output: Contribution to journalArticle

Kanda, Atsuhiro ; Noda, Kousuke ; Yuki, Kenya ; Ozawa, Yoko ; Furukawa, Takahisa ; Ichihara, Atsuhiro ; Ishida, Susumu. / Atp6ap2/(Pro)renin receptor interacts with Par3 as a cell polarity determinant required for laminar formation during retinal development in mice. In: Journal of Neuroscience. 2013 ; Vol. 33, No. 49. pp. 19341-19351.
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AU - Kanda, Atsuhiro

AU - Noda, Kousuke

AU - Yuki, Kenya

AU - Ozawa, Yoko

AU - Furukawa, Takahisa

AU - Ichihara, Atsuhiro

AU - Ishida, Susumu

PY - 2013

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