Serotonin (5-HT) is a major neurotransmitter in mammalian brains and is involved in brain development and psychiatric disorders. The 5-HT 1A receptor (5-HT 1A R) is a G-protein-coupled receptor (GPCR) associated with an inhibitory G-protein (G i ) with the widest and most abundant expression. It is not known; however, how expression or activity of 5-HT lA R is regulated. We studied here phosphorylation of 5-HT 1A R by cyclin-dependent kinase 5 (Cdk5), a neuron-specific membrane-bound Ser/Thr kinase that is activated by binding of the p35 Cdk5 activator. 5-HT 1A R was phosphorylated by the Cdk5–p35 complex at Thr314 in the third cytoplasmic loop. The phosphorylation stimulated the degradation of 5-HT 1A R by the proteasome, resulting in neutralization of the inhibitory action of 5-HT 1A R on intracellular cAMP concentration. These results suggest that Cdk5–p35 modulates 5-HT signaling through phosphorylation-dependent degradation of 5-HT lA R.
|ジャーナル||Biochemical and Biophysical Research Communications|
|出版ステータス||Published - 2019 3月 12|
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