Coupling profile of the metabotropic glutamate receptor 1α is regulated by the C-terminal domain
Coupling profile of the metabotropic glutamate receptor 1α is regulated by the C-terminal domain
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DOI：
10.1016/j.mcn.2006.11.021
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发表时间：
2007-03-01
影响因子：
3.5
通讯作者：
Kubo, Yoshihiro
中科院分区：
文献类型：
--
作者：
Tateyama, Michihiro;Kubo, Yoshihiro
代谢型谷氨酸受体Lot(mCluR1α)通过与不同类型的G蛋白偶联而引起不同的细胞反应。通过结合使用荧光指示剂，我们同时观察到mGluR1α的双重信号，通过激活Gq和Gs蛋白，分别随着细胞内钙离子和cAMP浓度的增加而增加。由于短剪接变异体mGluRIP不能激活Gs途径，所以双重信号由mGluRloL的长C-末端结构域调节。已知与长C末端尾巴相互作用的细胞骨架蛋白，如Hmer 1和4.1G，可调节mGluR1α信号；然而，它们对双重信号的影响尚不清楚。同时监测表明，4.1G通过与位于靠近Gs偶联重要区域的远端C-尾部的一簇酸性残基相互作用，起到双重信号调节作用，而不是简单的抑制作用。(C)2006 Elsevier Inc.保留所有权利。
The metabotropic glutamate receptor lot (mCluR1 alpha) is known to cause various cell responses via coupling with different types of G protein. By using a combination of fluorescent indicators, we simultaneously observed the dual signals of mGluR1 alpha, via activation of the Gq and Gs proteins, as increases in the intracellular Ca2+ and cAMP concentration, respectively. The dual signals are regulated by long C-terminal domain of mGluRloL since a short splice variant, mGluRIP, could not activate the Gs pathway. Cytoskeletal proteins that interact with the long C-terminal tail, such as homer1 and 4.1G, are known to modulate the mGluR1 alpha signaling; however, their effects on the dual signaling remain unknown. The simultaneous monitoring demonstrated that the 4.1G behaves as a regulator of dual signaling rather than a simple inhibitor, via its interaction with a cluster of acidic residues in the distal C-tail, which locates close to the important regions for the Gs coupling. (c) 2006 Elsevier Inc. All rights reserved.