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

doi:10.1016/j.bbrc.2019.01.093

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 journal › Article › peer-review

4 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	370-375
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	510
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2019.01.093
Publication status	Published - 2019 Mar 12
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

Access to Document

10.1016/j.bbrc.2019.01.093

Cite this

Takahashi, M., Kobayashi, Y., Ando, K., Saito, Y., & Hisanaga, S. I. (2019). Cyclin-dependent kinase 5 promotes proteasomal degradation of the 5-HT _1A receptor via phosphorylation Biochemical and Biophysical Research Communications, 510(3), 370-375. https://doi.org/10.1016/j.bbrc.2019.01.093

Cyclin-dependent kinase 5 promotes proteasomal degradation of the 5-HT _1A receptor via phosphorylation . / Takahashi, Miyuki; Kobayashi, Yuki; Ando, Kanae et al.
In: Biochemical and Biophysical Research Communications, Vol. 510, No. 3, 12.03.2019, p. 370-375.

Research output: Contribution to journal › Article › peer-review

Takahashi, M, Kobayashi, Y, Ando, K, Saito, Y & Hisanaga, SI 2019, ' Cyclin-dependent kinase 5 promotes proteasomal degradation of the 5-HT _1A receptor via phosphorylation ', Biochemical and Biophysical Research Communications, vol. 510, no. 3, pp. 370-375. https://doi.org/10.1016/j.bbrc.2019.01.093

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abstract = " 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. ",

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author = "Miyuki Takahashi and Yuki Kobayashi and Kanae Ando and Yumiko Saito and Hisanaga, {Shin ichi}",

note = "Funding Information: We would like to thank Dr. Paul R. Albert at University of Ottawa for providing 5-HT 1A R expression plasmid. This work was supported in part by a grant-in-aid of MEXT in Japan (grant number 16K07060 ). Publisher Copyright: {\textcopyright} 2019 The Authors",

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