Structural and functional insights into transmembrane AMPA receptor regulatory protein complexes.
Structural and functional insights into transmembrane AMPA receptor regulatory protein complexes.
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跨膜 AMPA 受体调节蛋白复合物的结构和功能见解。
DOI：
10.1085/jgp.201812264
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Sobolevsky,AlexanderI
中科院分区：
文献类型：
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作者：
Twomey,EdwardC;Yelshanskaya,MariaV;Sobolevsky,AlexanderI
快速兴奋性神经传递由离子型谷氨酸受体 (AMPAR) 的 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸 (AMPA) 亚型介导。 AMPAR 响应神经递质谷氨酸的结合，允许阳离子通过其离子通道孔进入，从而启动突触后神经元的去极化。 AMPAR 功能受到辅助亚基的显着影响，辅助亚基是调节蛋白，在整个大脑中与 AMPAR 形成各种复合物。研究最深入的辅助亚基是跨膜 AMPAR 调节蛋白 (TARP)，它改变 AMPAR 的组装、运输、定位、动力学和药理学。最近对 TARP 和 TARP 折叠生殖细胞特异性基因 1 样 (GSG1L) 亚基的结构和功能研究为辅助亚基如何调节突触复合体的功能提供了重要的线索。在这篇综述中，我们将这些最新的结构置于新的功能发现的背景下，以便深入了解 TARPs 调节 AMPAR 的决定因素。因此，我们揭示了为什么 TARP 表现出广泛的影响，尽管它们具有保守的模块化架构。
Fast excitatory neurotransmission is mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of ionotropic glutamate receptor (AMPAR). AMPARs initiate depolarization of the postsynaptic neuron by allowing cations to enter through their ion channel pores in response to binding of the neurotransmitter glutamate. AMPAR function is dramatically affected by auxiliary subunits, which are regulatory proteins that form various complexes with AMPARs throughout the brain. The most well-studied auxiliary subunits are the transmembrane AMPAR regulatory proteins (TARPs), which alter the assembly, trafficking, localization, kinetics, and pharmacology of AMPARs. Recent structural and functional studies of TARPs and the TARP-fold germ cell-specific gene 1-like (GSG1L) subunit have provided important glimpses into how auxiliary subunits regulate the function of synaptic complexes. In this review, we put these recent structures in the context of new functional findings in order to gain insight into the determinants of AMPAR regulation by TARPs. We thus reveal why TARPs display a broad range of effects despite their conserved modular architecture.