Induction of dendritic spines by an extracellular domain of AMPA receptor subunit GluR2
Induction of dendritic spines by an extracellular domain of AMPA receptor subunit GluR2
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DOI：
10.1038/nature01781
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发表时间：
2003-08-07
期刊：
影响因子：
64.8
通讯作者：
Sheng, M
中科院分区：
文献类型：
--
作者：
Passafaro, M;Nakagawa, T;Sheng, M
哺乳动物脑兴奋性神经细胞的突触传递主要由位于树突棘表面的AMPA （α -氨基-3-羟基-5-甲基-4-异恶唑丙酸）型谷氨酸受体介导。突触后AMPA受体的丰度与突触的大小和树突棘头的尺寸相关（1-4）。此外，长时程增强与树突棘的形成以及AMPA受体的突触传递有关（5-8）。协调AMPA受体传递和脊柱形态发生的分子机制尚不清楚。本研究表明，AMPA受体的谷氨酸受体2 （GluR2）亚基的过度表达增加了海马神经元中棘的大小和密度，更显著的是，在通常缺乏棘的释放gaba的中间神经元中诱导棘的形成。GluR2的细胞外n端结构域（NTD）负责这种作用，GluR2 NTD的异源融合蛋白抑制脊柱形态发生。我们认为GluR2的NTD作为受体-配体相互作用的一部分在细胞表面起作用，这对脊柱生长和/或稳定性很重要。
Synaptic transmission from excitatory nerve cells in the mammalian brain is largely mediated by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-type glutamate receptors located at the surface of dendritic spines. The abundance of postsynaptic AMPA receptors correlates with the size of the synapse and the dimensions of the dendritic spine head(1-4). Moreover, long-term potentiation is associated with the formation of dendritic spines as well as synaptic delivery of AMPA receptors(5-8). The molecular mechanisms that coordinate AMPA receptor delivery and spine morphogenesis are unknown. Here we show that overexpression of the glutamate receptor 2 (GluR2) subunit of AMPA receptors increases spine size and density in hippocampal neurons, and more remarkably, induces spine formation in GABA-releasing interneurons that normally lack spines. The extracellular N-terminal domain (NTD) of GluR2 is responsible for this effect, and heterologous fusion proteins of the NTD of GluR2 inhibit spine morphogenesis. We propose that the NTD of GluR2 functions at the cell surface as part of a receptor-ligand interaction that is important for spine growth and/or stability.