Receptor-Selective Diffusion Barrier Enhances Sensitivity of Astrocytic Processes to Metabotropic Glutamate Receptor Stimulation
Receptor-Selective Diffusion Barrier Enhances Sensitivity of Astrocytic Processes to Metabotropic Glutamate Receptor Stimulation
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DOI：
10.1126/scisignal.2002498
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发表时间：
2012-04-03
影响因子：
7.3
通讯作者：
Mikoshiba, Katsuhiko
中科院分区：
文献类型：
--
作者：
Arizono, Misa;Bannai, Hiroko;Mikoshiba, Katsuhiko
星形胶质细胞过程中代谢型谷氨酸受体（mGluR）依赖性钙离子（Ca 2+）信号传导调节突触传递和脑功能所必需的局部血流。然而，由于成像星形胶质细胞的过程中的困难，亚细胞的空间组织的mGluR依赖的Ca 2+信号还没有得到很好的表征，其调控机制仍然不清楚。使用遗传编码的Ca 2+指标，我们发现，尽管全球刺激mGluR激动剂，星形胶质细胞的过程本质上表现出显着的富集Ca 2+的反应。免疫细胞化学结果表明，这些极化的Ca 2+反应可归因于相对于索马的突起上的表面mGluR 5的密度增加。单粒子跟踪表面mGluR 5动力学揭示了一个膜屏障，阻止mGluR 5之间的进程和索马的运动。过表达mGluR或其羧基末端的表达使mGluR 5能够在索马和突起之间扩散，破坏mGluR 5和mGluR依赖性Ca 2+信号传导的极化。总之，我们的研究结果表明，mGluR 5-选择性扩散屏障之间的进程和索马，划分mGluR钙信号在星形胶质细胞，并可能允许控制突触和血管活性在特定的亚细胞结构域。
Metabotropic glutamate receptor (mGluR)-dependent calcium ion (Ca2+) signaling in astrocytic processes regulates synaptic transmission and local blood flow essential for brain function. However, because of difficulties in imaging astrocytic processes, the subcellular spatial organization of mGluR-dependent Ca2+ signaling is not well characterized and its regulatory mechanism remains unclear. Using genetically encoded Ca2+ indicators, we showed that despite global stimulation by an mGluR agonist, astrocyte processes intrinsically exhibited a marked enrichment of Ca2+ responses. Immunocytochemistry indicated that these polarized Ca2+ responses could be attributed to increased density of surface mGluR5 on processes relative to the soma. Single-particle tracking of surface mGluR5 dynamics revealed a membrane barrier that blocked the movement of mGluR5 between the processes and the soma. Overexpression of mGluR or expression of its carboxyl terminus enabled diffusion of mGluR5 between the soma and the processes, disrupting the polarization of mGluR5 and of mGluR-dependent Ca2+ signaling. Together, our results demonstrate an mGluR5-selective diffusion barrier between processes and soma that compartmentalized mGluR Ca2+ signaling in astrocytes and may allow control of synaptic and vascular activity in specific subcellular domains.