| First Author | Riediger F | Year | 2011 |
| Journal | J Am Soc Nephrol | Volume | 22 |
| Issue | 12 | Pages | 2193-202 |
| PubMed ID | 22034640 | Mgi Jnum | J:232697 |
| Mgi Id | MGI:5779933 | Doi | 10.1681/ASN.2011020200 |
| Citation | Riediger F, et al. (2011) Prorenin receptor is essential for podocyte autophagy and survival. J Am Soc Nephrol 22(12):2193-202 |
| abstractText | 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. |
