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Prorenin receptor is essential for podocyte autophagy and survival

Authors

  • F. Riediger
  • I. Quack
  • F. Qadri
  • B. Hartleben
  • J.K. Park
  • S.A. Potthoff
  • D. Sohn
  • G. Sihn
  • A. Rousselle
  • V. Fokuhl
  • U. Maschke
  • B. Purfuerst
  • W. Schneider
  • L.C. Rump
  • F.C. Luft
  • R. Dechend
  • M. Bader
  • T.B. Huber
  • G. Nguyen
  • D.N. Mueller

Journal

  • Journal of the American Society of Nephrology

Citation

  • J Am Soc Nephrol 22 (12): 2193-2202

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.


DOI

doi:10.1681/ASN.2011020200