Roh Seung-Eon, Hong Yun Hwa, Jang Dong Cheol, Kim Jun, Kim Sang Jeong
Department of Physiology, Seoul National University College of Medicine, 28, Yeongeon-dong, Jongno-gu, Seoul 110-799, Korea.
Mol Brain. 2014 Feb 10;7:9. doi: 10.1186/1756-6606-7-9.
Group I metabotropic glutamate receptors (mGlu1/5 receptors) have important roles in synaptic activity in the central nervous system. They modulate neuronal excitability by mobilizing intracellular Ca2+ following receptor activation. Also, accumulating evidence has indicated the association of Ca2+ signaling with lipid rafts. Caveolin, an adaptor protein found in a specialized subset of lipid rafts, has been reported to promote the localization of membrane proteins to lipid rafts.
In the present study, we investigated the role of lipid rafts on the mGlu1α receptor-mediated Ca2+ signaling in association with caveolin in hippocampal primary neurons and HEK293 cells. We show that the disruption of lipid rafts using methyl-β-cyclodextrin markedly decreased mGlu1α receptor-mediated Ca2+ transients and lipid rafts localization of the receptor. Furthermore, transfection of mGlu1α receptor with mutated caveolin-binding domain reduced localization of the receptor to lipid rafts. Also, application of a peptide blocker of mGlu1α receptor and caveolin binding reduced the Ca2+ signaling and the lipid rafts localization.
Taken together, these results suggest that the binding of mGlu1α receptor to caveolin is crucial for its lipid rafts localization and mGlu1α receptor-mediated Ca2+ transients.
I 型代谢型谷氨酸受体（mGlu1/5 受体）在中枢神经系统的突触活动中发挥重要作用。它们在受体激活后通过动员细胞内 Ca2+来调节神经元兴奋性。此外，越来越多的证据表明 Ca2+信号传导与脂筏有关。小窝蛋白是一种在脂筏的特定亚群中发现的衔接蛋白，据报道它能促进膜蛋白定位于脂筏。
在本研究中，我们研究了脂筏在海马原代神经元和 HEK293 细胞中与小窝蛋白相关的 mGlu1α 受体介导的 Ca2+信号传导中的作用。我们发现，使用甲基-β-环糊精破坏脂筏会显著降低 mGlu1α 受体介导的 Ca2+瞬变以及该受体在脂筏中的定位。此外，用突变的小窝蛋白结合结构域转染 mGlu1α 受体可降低该受体在脂筏中的定位。而且，应用 mGlu1α 受体和小窝蛋白结合的肽阻断剂可降低 Ca2+信号传导和脂筏定位。
综上所述，这些结果表明 mGlu1α 受体与小窝蛋白的结合对其在脂筏中的定位以及 mGlu1α 受体介导的 Ca2+瞬变至关重要。
