| First Author | Figueiredo M | Year | 2021 |
| Journal | Pflugers Arch | Volume | 473 |
| Issue | 8 | Pages | 1229-1246 |
| PubMed ID | 34228176 | Mgi Jnum | J:324585 |
| Mgi Id | MGI:7280814 | Doi | 10.1007/s00424-021-02598-z |
| Citation | Figueiredo M, et al. (2021) The (pro)renin receptor (ATP6ap2) facilitates receptor-mediated endocytosis and lysosomal function in the renal proximal tubule. Pflugers Arch 473(8):1229-1246 |
| abstractText | The ATP6ap2 (Pro)renin receptor protein associates with H(+)-ATPases which regulate organellar, cellular, and systemic acid-base homeostasis. In the kidney, ATP6ap2 colocalizes with H(+)-ATPases in various cell types including the cells of the proximal tubule. There, H(+)-ATPases are involved in receptor-mediated endocytosis of low molecular weight proteins via the megalin/cubilin receptors. To study ATP6ap2 function in the proximal tubule, we used an inducible shRNA Atp6ap2 knockdown rat model (Kd) and an inducible kidney-specific Atp6ap2 knockout mouse model. Both animal lines showed higher proteinuria with elevated albumin, vitamin D binding protein, and procathepsin B in urine. Endocytosis of an injected fluid-phase marker (FITC- dextran, 10 kDa) was normal whereas processing of recombinant transferrin, a marker for receptor-mediated endocytosis, to lysosomes was delayed. While megalin and cubilin expression was unchanged, abundance of several subunits of the H(+)-ATPase involved in receptor-mediated endocytosis was reduced. Lysosomal integrity and H(+)-ATPase function are associated with mTOR signaling. In ATP6ap2, KO mice mTOR and phospho-mTOR appeared normal but increased abundance of the LC3-B subunit of the autophagosome was observed suggesting a more generalized impairment of lysosomal function in the absence of ATP6ap2. Hence, our data suggests a role for ATP6ap2 for proximal tubule function in the kidney with a defect in receptor-mediated endocytosis in mice and rats. |
