突触BMAL1酸化控制着昼夜的海马体可塑性
Ilaria Barone1, Nicole M Gilette1, Hannah Hawks-Mayer1
1Department of Neurology and F.M. Kirby Center for Neurobiology, Boston Children's Hospital, Boston, MA 02115, USA.
Science advances
|October 25, 2023
概括
昼夜钟蛋白BMAL1被重新分配到突触中,通过控制CaMKIIα活动来调节记忆形成. 这种化BMAL1 (pBMAL1 ((S42)) 的突触局部化关闭了大脑可塑性的日常时间.
科学领域:
- 时间生物学 时间生物学
- 神经科学是一个神经科学.
- 分子生物学分子生物学
背景情况:
- 昼夜节律显著影响认知功能,包括长期记忆.
- 连接昼夜时钟与突触可塑性的分子机制尚未完全理解.
- 核心昼夜时钟依赖于涉及BMAL1转录因子的转录-翻译反循环 (TTFL).
研究的目的:
- 研究昼夜钟蛋白BMAL1在突触功能和记忆中的作用.
- 阐明生物节律影响突触可塑性的分子机制.
主要方法:
- 研究了BMAL1对海马突触的节奏局部化.
- 研究了BMAL1在Ser42 (pBMAL1(S42) 中的酸化在突触过程中的作用.
- 评估了pBMAL1(S42) 对CaMKIIα自酸化和CaMKIIα依赖的分子相互作用和长期强化 (LTP) 的影响.
主要成果:
- BMAL1以节奏的方式定位到海马突触,这取决于其在Ser42 (pBMAL1(S42) 的酸化.
- pBMAL1(S42) 调节突触 CaMKIIα 的自酸化.
- 基于CaMKIIα的分子相互作用和LTP的循环节律由pBMAL1(S42) 控制,而全球休息/活动行为不受影响.
结论:
- 该研究提出了一个模型,其中BMAL1被重新分配到突触,以局部调节突触可塑性的昼夜时间.
- 突触BMAL1,特别是其酸化形式,在根据一天中的时间关闭记忆形成过程中起着至关重要的作用.
- 这些发现揭示了连接中央昼夜时钟与突触层次认知功能的新机制.
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