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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

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Title: Atp6ap2/(Pro)renin Receptor Interacts with Par3 as a Cell Polarity Determinant Required for Laminar Formation during Retinal Development in Mice
Authors: Kanda, Atsuhiro Browse this author →KAKEN DB
Noda, Kousuke Browse this author →KAKEN DB
Yuki, Kenya Browse this author
Ozawa, Yoko Browse this author
Furukawa, Takahisa Browse this author
Ichihara, Atsuhiro Browse this author
Ishida, Susumu Browse this author →KAKEN DB
Issue Date: 4-Dec-2013
Publisher: Soc neuroscience
Journal Title: Journal of neuroscience
Volume: 33
Issue: 49
Start Page: 19341
End Page: 19351
Publisher DOI: 10.1523/JNEUROSCI.1362-13.2013
PMID: 24305829
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 tissue RAS activation, A tp6ap2/(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.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 石田 晋

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