TY - JOUR
T1 - Prorenin Receptor Is Essential for Normal Podocyte Structure and Function
AU - Oshima, Y
AU - Kinouchi, K
AU - Ichihara, A
AU - Sakoda, M
AU - Kurauchi-Mito, A
AU - Bokuda, K
AU - Narita, T
AU - Kurosawa, H
AU - Sun-Wada, GH
AU - Wada, Y
AU - Yamada, T
AU - Takemoto, M
AU - Saleem, MA
AU - Quaggin, SE
AU - Itoh, H
PY - 2011/11
Y1 - 2011/11
N2 - 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.
AB - 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.
M3 - Article (Academic Journal)
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
SN - 1046-6673
ER -