前突触神经素-3的替代拼接通过突触控制了后突触AMPA受体的贩运
Jason Aoto1, David C Martinelli, Robert C Malenka
1Department of Molecular and Cellular Physiology, Stanford University Medical School, 265 Campus Drive, CA 94305-5453, USA.
Cell
|July 6, 2013
概括
神经素替代拼接控制了后突触AMPA受体水平和贩运. 这揭示了调节突触强度和可塑性的新机制,影响了自闭症和精神分裂症等疾病.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 神经素是关键的前突触细胞粘附分子,与精神分裂症和自闭症等神经系统疾病有关.
- 神经素替代拼接是广泛的,其生理学意义仍然不完全理解.
- 神经素-3的序列4 (SS4) 是高度调节的,并影响与突触后连接体的相互作用.
研究的目的:
- 调查neurexin-3替代拼接的生理作用,特别是SS4的加入.
- 确定SS4纳入如何影响突触功能和可塑性.
主要方法:
- 产生诺金小鼠,条件包括/切除神经素-3 SS4.
- 对 postsynaptic AMPA 和 NMDA 受体水平的分析.
- 在长期强化 (LTP) 期间评估AMPA受体内细胞结核和招募.
主要成果:
- 构成性纳入神经素-3 SS4 降低了突触后AMPA受体水平.
- 加入SS4增强了后突触AMPA受体内细胞增强.
- 在依赖NMDA受体的LTP过程中,神经素-3 SS4废止了后突触AMPA受体的招募.
- 通过选择性切除SS4来挽救表型.
结论:
- 预突触神经素-3的替代拼接直接控制了后突触AMPA受体的贩运.
- 这突显了一种意想不到的跨突触调节机制,影响突触强度和可塑性.
- 这些发现提供了与神经素功能障碍相关的神经系统疾病的分子基础的见解.
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