AMPA receptor tetramerization is mediated by Q/R editing
AMPA receptor tetramerization is mediated by Q/R editing
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DOI：
10.1016/s0896-6273(03)00668-8
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发表时间：
2003-11-13
期刊：
影响因子：
16.2
通讯作者：
Ziff, EB
中科院分区：
文献类型：
--
作者：
Greger, IH;Khatri, L;Ziff, EB
AMPA型谷氨酸受体（AMPAR）在兴奋性突触传递和可塑性中起重要作用。通道特性主要由其四个亚基GluR 1 -4（或A-D）的组成决定。在这里，我们表明，AMPAR组装和亚基化学计量是由RNA编辑的孔环。我们证明了在GluR 2 Q/R位点的编辑调节AMPAR组装在四聚化的步骤。具体而言，编辑的R亚基大部分未组装，ER保留，而未编辑的Q亚基容易四聚化，并运输到突触。这种组装机制限制了AMPAR四聚体中功能关键的R亚基的数量。因此，单个氨基酸残基影响通道组成，进而控制通过大脑中大多数AMPAR的离子传导。
AMPA-type glutamate receptors (AMPARs) play a major role in excitatory synaptic transmission and plasticity. Channel properties are largely dictated by their composition of the four subunits, GluR1-4 (or A-D). Here we show that AMPAR assembly and subunit stoichiometry are determined by RNA editing in the pore loop. We demonstrate that editing at the GluR2 Q/R site regulates AMPAR assembly at the step of tetramerization. Specifically, edited R subunits are largely unassembled and ER retained, whereas unedited Q subunits readily tetramerize, and traffic to synapses. This assembly mechanism restricts the number of the functionally critical R subunits in AMPAR tetramers. Therefore, a single amino acid residue affects channel composition and, in turn, controls ion conduction through the majority of AMPARs in the brain.