| First Author | Okamoto T | Year | 2020 |
| Journal | Biochem Biophys Res Commun | Volume | 521 |
| Issue | 4 | Pages | 1030-1035 |
| PubMed ID | 31732153 | Mgi Jnum | J:298533 |
| Mgi Id | MGI:6480224 | Doi | 10.1016/j.bbrc.2019.11.001 |
| Citation | Okamoto T, et al. (2020) Hypertonicity-responsive ubiquitin ligase RNF183 promotes Na, K-ATPase lysosomal degradation through ubiquitination of its beta1 subunit. Biochem Biophys Res Commun 521(4):1030-1035 |
| abstractText | We previously reported that RNF183, a member of the RING finger (RNF) protein family, is specifically expressed in the renal collecting duct and that RNF183 mRNA is induced by the activity of nuclear factor of activated T cells 5 (NFAT5), which regulates the transcription of essential proteins for adaptation to hypertonic conditions. The renal medulla is the only tissue that is continuously hypertonic; therefore, RNF183 possibly plays an important role in adaptation to continuous hypertonic conditions. However, the mechanism of how cells adapt to long-term hypertonicity via RNF183 remains unclear. In this study, the Na, K-ATPase alpha1 subunit was identified as a candidate substrate of RNF183 by the BirA proximity-biotinylation technique. The Na, K-ATPase alpha1 subunit acts as an ion transporter along with the Na, K-ATPase beta1 subunit at the plasma membrane. We confirmed that RNF183 interacted with both alpha1 and beta1 subunits; however, we found that RNF183 ubiquitinated only the beta1 subunit, not the alpha1 subunit. Furthermore, RNF183 translocated both alpha1 and beta1 subunits from the plasma membrane to lysosomes. In addition, the expression levels of alpha1 and beta1 subunits in HEK293cells stably expressing RNF183 were significantly decreased compared with mock control cells, and were restored by siRNA-mediated knockdown of RNF183. Moreover, in RNF183-expressing cells, chloroquine treatment increased the protein levels of the alpha1 and beta1 subunits. Therefore, our results suggest that Na, K-ATPase alpha1 and beta1 subunits are degraded in lysosomes by RNF183-mediated ubiquitination of beta1 subunit. |
