Prorenin receptor is essential for normal podocyte structure and function.

Abstract

The prorenin receptor is an accessory subunit of the vacuolar H(+)-ATPase, suggesting that it has fundamental functions beyond activation of the local renin-angiotensin system. Podocytes express the prorenin receptor, but its function in these cells is unknown. Here, podocyte-specific, conditional, prorenin receptor-knockout mice died of kidney failure and severe proteinuria within 4 weeks of birth. The podocytes of these mice exhibited foot process effacement with reduced and altered localization of the slit-diaphragm proteins nephrin and podocin. Furthermore, the podocytes contained numerous autophagic vacuoles, confirmed by enhanced accumulation of microtubule-associated protein 1 light chain 3-positive intracellular vesicles. Ablation of the prorenin receptor selectively suppressed expression of the V(0) c-subunit of the vacuolar H(+)-ATPase in podocytes, resulting in deacidification of intracellular vesicles. In conclusion, the prorenin receptor is important for the maintenance of normal podocyte structure and function.

• Authors: Yoichi Oshima, Kenichiro Kinouchi, Atsuhiro Ichihara, Mariyo Sakoda, Asako Kurauchi-Mito, Kanako Bokuda, Tatsuya Narita, Hideaki Kurosawa, Ge-Hong Sun-Wada, Yoh Wada, Taketo Yamada, Minoru Takemoto, Moin A Saleem, Susan E Quaggin, Hiroshi Itoh
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 22 Issue 12 Pg. 2203-12 (Dec 2011) ISSN: 1533-3450 [Electronic] United States
• PMID: 22052048 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Cell Surface
• Prorenin Receptor

Topics

• Animals
• Cell Death
• Mice
• Podocytes (physiology, ultrastructure)
• Receptors, Cell Surface (physiology)
• Prorenin Receptor