| First Author | Lu Q | Year | 2020 |
| Journal | FEBS Lett | Volume | 594 |
| Issue | 11 | Pages | 1787-1796 |
| PubMed ID | 32134507 | Mgi Jnum | J:305754 |
| Mgi Id | MGI:6705334 | Doi | 10.1002/1873-3468.13765 |
| Citation | Lu Q, et al. (2020) 1-Stearoyl-2-docosahexaenoyl-phosphatidic acid interacts with and activates Praja-1, the E3 ubiquitin ligase acting on the serotonin transporter in the brain. FEBS Lett 594(11):1787-1796 |
| abstractText | Serotonin transporter (SERT) is involved in serotonergic system regulation and in the pathophysiology/therapeutics of serotonin-/SERT-related diseases such as obsessive-compulsive disorder, depression, autism, and schizophrenia. We recently revealed that diacylglycerol (DG) kinase (DGK) delta induces ubiquitination/degradation of SERT in a DGK activity-dependent manner through Praja-1 E3 ubiquitin-protein ligase. However, it is still unclear how Praja-1 activity is regulated by DGKdelta. Here, we reveal that 1-stearoyl-2-docosahexaenoyl (18:0/22:6)-phosphatidic acid (PA) and 18:0/22:6-DG are simultaneously decreased and accumulated, respectively, in the DGKdelta-knockout mouse brain, indicating that DGKdelta selectively phosphorylates 18:0/22:6-DG to generate 18:0/22:6-PA. Moreover, we find that 18:0/22:6-PA selectively binds to Praja-1 and enhances its activity. These results strongly suggest that 18:0/22:6-PA generated by DGKdelta activates Praja-1 to degrade SERT in the brain. |
