Coordination chemogenetics for activation of GPCR-type glutamate receptors in brain tissue

Kento Ojima, Wataru Kakegawa, Tokiwa Yamasaki, Yuta Miura, Masayuki Itoh, Yukiko Michibata, Ryou Kubota, Tomohiro Doura, Eriko Miura, Hiroshi Nonaka, Seiya Mizuno, Satoru Takahashi, Michisuke Yuzaki, Itaru Hamachi, Shigeki Kiyonaka

研究成果: Article査読

1 被引用数 (Scopus)

抄録

Direct activation of cell-surface receptors is highly desirable for elucidating their physiological roles. A potential approach for cell-type-specific activation of a receptor subtype is chemogenetics, in which both point mutagenesis of the receptors and designed ligands are used. However, ligand-binding properties are affected in most cases. Here, we developed a chemogenetic method for direct activation of metabotropic glutamate receptor 1 (mGlu1), which plays essential roles in cerebellar functions in the brain. Our screening identified a mGlu1 mutant, mGlu1(N264H), that was activated directly by palladium complexes. A palladium complex showing low cytotoxicity successfully activated mGlu1 in mGlu1(N264H) knock-in mice, revealing that activation of endogenous mGlu1 is sufficient to evoke the critical cellular mechanism of synaptic plasticity, a basis of motor learning in the cerebellum. Moreover, cell-type-specific activation of mGlu1 was demonstrated successfully using adeno-associated viruses in mice, which shows the potential utility of this chemogenetics for clarifying the physiological roles of mGlu1 in a cell-type-specific manner.

本文言語English
論文番号3167
ジャーナルNature communications
13
1
DOI
出版ステータスPublished - 2022 12月

ASJC Scopus subject areas

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 一般
  • 物理学および天文学(全般)

フィンガープリント

「Coordination chemogenetics for activation of GPCR-type glutamate receptors in brain tissue」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル