Qiang Lu, Chiaki Murakami, Yuki Murakami, Fumi Hoshino, Maho Asami, Takako Usuki, Hiromichi Sakai, Fumio Sakane
FEBS letters 2020 JunSerotonin 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) δ 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 DGKδ. 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 DGKδ-knockout mouse brain, indicating that DGKδ 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 DGKδ activates Praja-1 to degrade SERT in the brain. © 2020 Federation of European Biochemical Societies.
Qiang Lu, Chiaki Murakami, Yuki Murakami, Fumi Hoshino, Maho Asami, Takako Usuki, Hiromichi Sakai, Fumio Sakane. 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 letters. 2020 Jun;594(11):1787-1796
PMID: 32134507
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