Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
J Neurosci. 2010 Jan 20;30(3):1064-72. doi: 10.1523/JNEUROSCI.3909-09.2010.
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.
谷氨酸是脊椎动物大脑中的主要兴奋性神经递质。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，并作为天然离子通道发挥作用。然而，AMPA 受体和 TARP 复合物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该蛋白复合物的组装和化学计量，发现功能性 AMPA 受体确实以二聚体-二聚体结构组装为四聚体。此外，我们发现 AMPA 受体辅助亚基 TARP 在 AMPA 受体上具有可变的化学计量（1-4 个 TARP 单位），并且 1 个 TARP 单位足以调节 AMPA 受体活性。在神经元中，TARP 在 AMPA 受体上具有固定的最小化学计量。AMPA 受体/TARP 复合物的这种基本组成对于阐明突触传递所依赖的分子机制非常重要。
