依赖格林受体的海马体多巴胺/DRD1信号
Andras Kern1, Maria Mavrikaki1, Celine Ullrich1
1Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 33458, USA.
Cell
|November 23, 2015
概括
格林受体 (GHSR1a) 与多巴胺受体-1 (DRD1) 相互作用,以启动海马突触可塑性和记忆,独立于cAMP信号.
科学领域:
- 神经科学
- 分子生物学
- 细胞信号传输
背景情况:
- 格林受体 (GHSR1a) 和多巴胺受体-1 (DRD1) 在海马神经元中共同表达.
- 格林在海马体中是不可检测的,这表明阿波-GHSR1a (无体受体) 的作用.
研究的目的:
- 研究海马神经元中的apo-GHSR1a的功能.
- 阐明DRD1介导的海马突触可塑性的信号机制.
主要方法:
- 实时单分子分析和海马神经元的近距离测量.
- 在小鼠中对GHSR1a的遗传和药理失活.
- 评估DRD1介导的海马行为和记忆.
主要成果:
- Apo-GHSR1a与DRD1形成二元体,由DRD1激动增强,以及与DRD1和Gαq预组合的异构体复合体.
- 激活DRD1会触发非正规的Gαq-PLC-IP3-Ca2+信号,绕过正规的Gαs-cAMP通路.
- 这种非正规的途径导致CaMKII激活,谷氨酸受体外细胞分裂,突触重组和突触可塑性标记.
- GHSR1a的失活阻断了这种途径,并损害了DRD1介导的海马行为和记忆.
结论:
- GHSR1a对于DRD1启动的海马突触可塑性和记忆非常重要.
- 一个涉及apo-GHSR1a:DRD1:Gαq复合体的新信号机制独立于cAMP调节海马功能.
- 这一发现揭示了apo-GHSR1a在突触可塑性和认知过程中以前未知的作用.
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