Cyclin-dependent kinase 5 promotes proteasomal degradation of the 5-HT 1A receptor via phosphorylation

Miyuki Takahashi, Yuki Kobayashi, Kanae Ando, Yumiko Saito, Shin ichi Hisanaga*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)370-375
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - 2019 Mar 12
Externally publishedYes


  • 5-HT
  • 5-HT R
  • Cdk5
  • Phosphorylation
  • Proteasomal degradation
  • Serotonin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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