Schoepfer R, Monyer H, Sommer B, Wisden W, Sprengel R, Kuner T, Lomeli H, Herb A, Köhler M, Burnashev N
Center for Molecular Biology, Heidelberg, Germany.
Prog Neurobiol. 1994 Feb;42(2):353-7. doi: 10.1016/0301-0082(94)90076-0.
The ligand-gated receptors for L-glutamate play a central role in acute neuronal degeneration. Recently cDNAs have been isolated for subunits of several glutamate receptor subtypes. By sequence homology all these subunits clearly belong to one large gene family. Several subfamilies exist and match roughly previously pharmacologically and electrophysiologically defined subtypes of glutamate receptors. Currently four genes (GluR A, B, C and D) are known that code for the AMPA subtypes of glutamate receptors. Recombinant expression of wild type and mutated sequences identified a critical residue in the putative TM2 channel-lining segment that controls Ca2+ ion permeability. The arginine (R) found in GluR B subunits at that position renders AMPA channels impermeable for Ca2+ ions, whereas glutamine (Q) containing GluR A, C and D subunits give rise to Ca2+ permeable channels. RNA editing converts the genomically encoded glutamine codon into the arginine codon found in GluR B cDNAs for the Q/R site. NMDA subtypes of glutamate receptors are formed after coexpression of the NR1 cDNA with a cDNA of the NR2 family. Depending on the member of the NR2 family used, NMDA receptors with different kinetical and pharmacological properties are generated. Common to all channels of these NMDA receptors is a high permeability for Ca2+ ions and a voltage dependent block by Mg2+ ions. All currently known NMDA receptor subunits have an asparagine at the Q/R homologous position. We found that this residue is critical for Mg2+ block and Ca2+ permeability of NMDA receptor channels.
L - 谷氨酸的配体门控受体在急性神经元变性中起核心作用。最近，已分离出几种谷氨酸受体亚型亚基的cDNA。通过序列同源性，所有这些亚基显然都属于一个大的基因家族。存在几个亚家族，大致与先前通过药理学和电生理学定义的谷氨酸受体亚型相匹配。目前已知有四个基因（GluR A、B、C和D）编码谷氨酸受体的AMPA亚型。野生型和突变序列的重组表达确定了假定的TM2通道内衬片段中一个控制Ca2 +离子通透性的关键残基。在该位置的GluR B亚基中发现的精氨酸（R）使AMPA通道对Ca2 +离子不可渗透，而含有谷氨酰胺（Q）的GluR A、C和D亚基则产生Ca2 +可渗透通道。RNA编辑将基因组编码的谷氨酰胺密码子转换为GluR B cDNA中在Q/R位点发现的精氨酸密码子。谷氨酸受体的NMDA亚型是在NR1 cDNA与NR2家族的cDNA共表达后形成的。根据所使用的NR2家族成员不同，会产生具有不同动力学和药理学特性的NMDA受体。这些NMDA受体的所有通道共同的特点是对Ca2 +离子具有高通透性以及被Mg2 +离子电压依赖性阻断。目前所有已知的NMDA受体亚基在Q/R同源位置都有一个天冬酰胺。我们发现该残基对NMDA受体通道的Mg2 +阻断和Ca2 +通透性至关重要。
