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^*

^*この研究の対応する著者

研究成果: Article › 査読

3 被引用数 (Scopus)

抄録

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.

本文言語	English
ページ（範囲）	370-375
ページ数	6
ジャーナル	Biochemical and Biophysical Research Communications
巻	510
号	3
DOI	https://doi.org/10.1016/j.bbrc.2019.01.093
出版ステータス	Published - 2019 3月 12
外部発表	はい

ASJC Scopus subject areas

生物理学
生化学
分子生物学
細胞生物学

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10.1016/j.bbrc.2019.01.093

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引用スタイル

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 その他.
In: Biochemical and Biophysical Research Communications, Vol. 510, No. 3, 12.03.2019, p. 370-375.

研究成果: Article › 査読

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. ",

keywords = "5-HT, 5-HT R, Cdk5, Phosphorylation, Proteasomal degradation, Serotonin",

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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AU - Hisanaga, Shin ichi

N1 - 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: © 2019 The Authors

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N2 - 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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Cyclin-dependent kinase 5 promotes proteasomal degradation of the 5-HT 1A receptor via phosphorylation

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Cyclin-dependent kinase 5 promotes proteasomal degradation of the 5-HT _1A receptor via phosphorylation