Different structural requirements for functional ion pore transplantation suggest different gating mechanisms of NMDA and kainate receptors
Different structural requirements for functional ion pore transplantation suggest different gating mechanisms of NMDA and kainate receptors
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功能性离子孔移植的不同结构要求表明 NMDA 和红藻氨酸受体的门控机制不同
DOI：
10.1111/j.1471-4159.2008.05623.x
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发表时间：
2008
影响因子：
4.7
通讯作者：
M. Hollmann
中科院分区：
文献类型：
--
作者：
C. Villmann;Jutta Hoffmann;M. Werner;S. Kott;N. Strutz‐Seebohm;Tanja Nilsson;M. Hollmann
虽然在表征高亲和力红藻氨酸（KA）受体亚基KA 1和KA 2的生理功能方面取得了相当大的进展，但尚未显示同源离子通道功能。在这项研究中采用离子通道移植方法来直接测试同源表达的KA 1和KA 2孔结构域是否能够传导电流。将KA 1或KA 2的离子孔移植到GluR 6中产生了功能完善的离子通道，其允许表征那些完全由KA 1或KA 2的离子孔确定的电生理和药理学性质。这第一次表明，KA 1和KA 2离子孔域本质上能够传导离子，即使在同质孔组件。NMDA受体类似于含有KA 1或KA 2的受体，仅作为异聚复合物发挥作用。它们由NR 1和NR 2亚基组成，当均聚表达时，它们都是无功能的。与NR 1相反，当移植到GluR 6中时，同聚体NR 2B离子孔未能将配体结合转化为孔开放。类似地，插入GluR 6的NR 1和NR 2的离子通道结构域的异聚体共表达未能产生功能通道。因此，我们的结论是，在强制性异四聚体NMDA受体的离子通道开放的机制显着不同，在facultimate异四聚体α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯和KA受体。
Although considerable progress has been made in characterizing the physiological function of the high‐affinity kainate (KA) receptor subunits KA1 and KA2, no homomeric ion channel function has been shown. An ion channel transplantation approach was employed in this study to directly test if homomerically expressed KA1 and KA2 pore domains are capable of conducting currents. Transplantation of the ion pore of KA1 or KA2 into GluR6 generated perfectly functional ion channels that allowed characterization of those electrophysiological and pharmacological properties that are determined exclusively by the ion pore of KA1 or KA2. This demonstrates for the first time that KA1 and KA2 ion pore domains are intrinsically capable of conducting ions even in homomeric pore assemblies. NMDA receptors, similar to KA1‐ or KA2‐containing receptors, function only as heteromeric complexes. They are composed of NR1 and NR2 subunits, which both are non‐functional when expressed homomerically. In contrast to NR1, the homomeric NR2B ion pore failed to translate ligand binding into pore opening when transplanted into GluR6. Similarly, heteromeric coexpression of the ion channel domains of both NR1 and NR2 inserted into GluR6 failed to produce functional channels. Therefore, we conclude that the mechanism underlying the ion channel opening in the obligatorily heterotetrameric NMDA receptors differs significantly from that in the facultatively heterotetrameric α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate and KA receptors.
DOI：
10.1073/pnas.90.2.755
发表时间：
1993-01-15
影响因子：
11.1
作者：
EGEBJERG, J;HEINEMANN, SF
通讯作者：
HEINEMANN, SF