NMDA receptor subunit composition controls synaptogenesis and synapse stabilization
NMDA receptor subunit composition controls synaptogenesis and synapse stabilization
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DOI：
10.1073/pnas.1012676108
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发表时间：
2011-04-05
影响因子：
11.1
通讯作者：
Barria, Andres
中科院分区：
文献类型：
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作者：
Gambrill, Abigail C.;Barria, Andres
在大鼠海马的出生后早期发育过程中，突触发生与NMDA受体亚基组成从NR 2B到NR 2A的发育转换平行发生。目前还不清楚这种开关如何影响突触发生、突触成熟和突触稳定的过程。我们研究了NR 2亚基在NR 2A蛋白的表达和突触结合开始通过达到成人水平的时间期间在突触发生中的作用。我们发现NR 2A在器官型海马切片中的早期表达减少了突触的数量以及棘的体积和动力学。相反，NR 2B的过表达不影响突触的正常数量和生长;然而，它确实增加了脊柱运动性，以更高的速度增加和缩回脊柱。NR 2B的C末端，特别是其结合CaMKII的能力，足以允许适当的突触形成和成熟。相反，NR 2A的C末端足以阻止突触数量和棘生长的发育。我们的研究结果表明，突触NR 2B NR 2A的比例控制脊柱运动和突触，并建议在招聘的信号和支架分子适当的突触所需的NR 2的细胞内C末端的结构作用。
During early postnatal development in the rat hippocampus, synaptogenesis occurs in parallel with a developmental switch in the subunit composition of NMDA receptors from NR2B to NR2A. It is unclear how this switch affects the process of synaptogenesis, synapse maturation, and synapse stabilization. We investigated the role of NR2 subunits in synaptogenesis during the period in which expression and synaptic incorporation of the NR2A protein begins through the time when it reaches adult levels. We found that early expression of NR2A in organotypic hippocampal slices reduces the number of synapses and the volume and dynamics of spines. In contrast, overexpression of NR2B does not affect the normal number and growth of synapses; however, it does increase spine motility, adding and retracting spines at a higher rate. The C terminus of NR2B, and specifically its ability to bind CaMKII, is sufficient to allow proper synapse formation and maturation. Conversely, the C terminus of NR2A was sufficient to stop the development of synapse number and spine growth. Our results indicate that the ratio of synaptic NR2B over NR2A controls spine motility and synaptogenesis, and suggest a structural role for the intracellular C terminus of NR2 in recruiting the signaling and scaffolding molecules necessary for proper synaptogenesis.