Prorenin receptor is essential for podocyte autophagy and survival

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Item Type:	Article
Title:	Prorenin receptor is essential for podocyte autophagy and survival
Creators Name:	Riediger, F., Quack, I., Qadri, F., Hartleben, B., Park, J.K., Potthoff, S.A., Sohn, D., Sihn, G., Rousselle, A., Fokuhl, V., Maschke, U., Purfürst, B., Schneider, W., Rump, L.C., Luft, F.C., Dechend, R., Bader, M., Huber, T.B., Nguyen, G. and Mueller, D.N.
Abstract:	The prorenin receptor (PRR) is highly expressed in podocytes, but its role in the maintenance of podocyte function is unknown. Here we generated podocyte-specific PRR-knockout mice and found that these animals died between 2 to 3 wk after birth. Within 14 d, PRR-knockout mice developed nephrotic syndrome, albuminuria with podocyte foot-process fusion, and cytoskeletal changes. Podocyte-specific PRR deletion also led to disturbed processing of multivesicular bodies and enrichment of autophagosomal (LC3) and lysosomal (LAMP2) markers, indicating a functional block in autophagosome-lysosome fusion and an overload of the proteasomal protein-degradation machinery. In vitro, PRR knockdown and pharmacologic blockade of vacuolar H(+)-ATPases, which associate with the PRR, increased vesicular pH, led to accumulation of LC3-positive and LAMP2-positive vesicles and altered the cytoskeleton. Taken together, these results suggest that the PRR is essential for podocyte function and survival by maintaining autophagy and protein-turnover machinery. Furthermore, PRR contributes to the control of lysosomal pH, which is important for podocyte survival and cytoskeletal integrity.
Keywords:	Autophagy, Cell Survival, Podocytes, Cell Surface Receptors, Animals, Mice
Source:	Journal of the American Society of Nephrology
ISSN:	1046-6673
Publisher:	American Society of Nephrology
Volume:	22
Number:	12
Page Range:	2193-2202
Date:	December 2011
Official Publication:	https://doi.org/10.1681/ASN.2011020200
PubMed:	View item in PubMed

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