Assembly and Stoichiometry of the AMPA Receptor and Transmembrane AMPA Receptor Regulatory Protein Complex
Assembly and Stoichiometry of the AMPA Receptor and Transmembrane AMPA Receptor Regulatory Protein Complex
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DOI：
10.1523/jneurosci.3909-09.2010
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发表时间：
2010-01-20
影响因子：
5.3
通讯作者：
Tomita, Susumu
中科院分区：
文献类型：
--
作者：
Kim, Kwang S.;Yan, Dan;Tomita, Susumu
谷氨酸是脊椎动物大脑中一种主要的兴奋性神经递质。AMPA型谷氨酸受体介导快速兴奋性传递。AMPA受体与跨膜AMPA受体调节蛋白(TARP)辅助亚基组装，发挥天然离子通道的作用。然而，AMPA受体和TARP复合体的组装和化学计量仍然不清楚。在这里，我们开发了一种新的策略来确定这种蛋白质复合体的组装和化学计量比，并发现功能性AMPA受体确实以四聚体的形式组装在二聚体结构中。此外，我们还发现AMPA受体辅助亚单位TARP在AMPA受体上具有不同的化学计量比(1-4个TARP单位)，并且1个TARP单位足以调节AMPA受体的活性。在神经元中，TARP对AMPA受体有固定的和最小的化学计量比。AMPA受体/TARP复合体的这种基本组成对于阐明突触传递的分子机制很重要。
Glutamate is a major excitatory neurotransmitter in the vertebrate brain. AMPA-type glutamate receptors mediate fast excitatory transmission. AMPA receptors assemble with transmembrane AMPA receptor regulatory protein ( TARP) auxiliary subunits and function as native ion channels. However, the assembly and stoichiometry of AMPA receptor and TARP complexes remain unclear. Here, we developed a novel strategy to determine the assembly and stoichiometry of this protein complex and found that functional AMPA receptors indeed assembled as a tetramer in a dimer-of-dimers structure. Furthermore, we found that the AMPA receptor auxiliary subunit, TARP, had a variable stoichiometry (1-4 TARP units) on AMPA receptors and that 1 TARP unit was sufficient to modulate AMPA receptor activity. In neurons, TARP had fixed and minimum stoichiometry on AMPA receptors. This fundamental composition of the AMPA receptor/TARP complex is important for the elucidation of the molecular machinery that underlies synaptic transmission.