| First Author | Nagarajan S | Year | 2017 |
| Journal | Mol Cell Endocrinol | Volume | 450 |
| Pages | 74-82 | PubMed ID | 28454724 |
| Mgi Jnum | J:255286 | Mgi Id | MGI:6104043 |
| Doi | 10.1016/j.mce.2017.04.020 | Citation | Nagarajan S, et al. (2017) Protein Phosphatase 1alpha enhances renal aldosterone signaling via mineralocorticoid receptor stabilization. Mol Cell Endocrinol 450:74-82 |
| abstractText | Stimulation of the mineralocorticoid receptor (MR) by aldosterone controls several physiological parameters including blood pressure, inflammation or metabolism. We previously showed that MR turnover constitutes a crucial regulatory step in the responses of renal epithelial cells to aldosterone. Here, we identified Protein Phosphatase 1 alpha (PP1alpha), as a novel cytoplasmic binding partner of MR that promotes the receptor activity. The RT-PCR expression mapping of PP1alpha reveals a high expression in the kidney, particularly in the distal part of the nephron. At the molecular level, we demonstrate that PP1alpha inhibits the ubiquitin ligase Mdm2 by dephosphorylation, preventing its interaction with MR. This results in the accumulation of the receptor due to reduction of its proteasomal degradation and consequently a greater aldosterone-induced Na(+) uptake by renal cells. Thus, our findings describe an original mechanism involving a phosphatase in the regulation of aldosterone signaling and provide new and important insights into the molecular mechanism underlying the MR turnover. |
