Journal
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Volume 22, Issue 12, Pages 2203-2212Publisher
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2011020202
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Funding
- Ministry of Education, Culture, Sports, Science and Technology [22390171]
- Grants-in-Aid for Scientific Research [21116002, 11J04266, 22390171, 21390286, 23570178] Funding Source: KAKEN
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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.
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