The Metabotropic Glutamate Receptor mGlu7 Activates Phospholipase C, Translocates Munc-13-1 Protein, and Potentiates Glutamate Release at Cerebrocortical Nerve Terminals
The Metabotropic Glutamate Receptor mGlu7 Activates Phospholipase C, Translocates Munc-13-1 Protein, and Potentiates Glutamate Release at Cerebrocortical Nerve Terminals
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DOI：
10.1074/jbc.m109.080838
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发表时间：
2010-06-04
影响因子：
4.8
通讯作者：
Sanchez-Prieto, Jose
中科院分区：
文献类型：
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作者：
Martin, Ricardo;Durroux, Thierry;Sanchez-Prieto, Jose
在突触结，代谢型谷氨酸受体7（mGlu 7受体）作为自身受体，抑制谷氨酸释放。在这种反应中，mGlu 7受体触发百日咳毒素敏感的G蛋白激活，减少突触前Ca 2+内流和随后的去极化诱发释放。在这里，我们报告说，受体耦合信号通路，增强释放可以看到神经末梢长期暴露于激动剂L-（+）-膦酰基丁酸，L-AP 4。这种新的mGlu 7受体反应涉及增加释放诱导的Ca 2+离子载体离子霉素，这表明一种机制，是独立的Ca 2+通道活性，但依赖于下游胞吐释放机械。mGlu 7受体介导的增强抵抗暴露于百日咳毒素，但依赖于磷脂酶C，并增加磷脂酰肌醇（4，5）-二磷酸水解。此外，释放的增强不依赖于蛋白激酶C，尽管它被二酰基甘油结合位点拮抗剂calphostin C阻断。我们还发现，活化mGlu 7受体易位的活性区蛋白质突触囊泡启动，munc 13 -1，从可溶性颗粒馏分。我们提出mGlu 7受体可以通过多种途径促进或抑制谷氨酸的释放，从而发挥突触前功能的稳态控制。
At synaptic boutons, metabotropic glutamate receptor 7 (mGlu7 receptor) serves as an autoreceptor, inhibiting glutamate release. In this response, mGlu7 receptor triggers pertussis toxin-sensitive G protein activation, reducing presynaptic Ca2+ influx and the subsequent depolarization evoked release. Here we report that receptor coupling to signaling pathways that potentiate release can be seen following prolonged exposure of nerve terminals to the agonist L-(+)-phosphonobutyrate, L-AP4. This novel mGlu7 receptor response involves an increase in the release induced by the Ca2+ ionophore ionomycin, suggesting a mechanism that is independent of Ca2+ channel activity, but dependent on the downstream exocytotic release machinery. The mGlu7 receptor-mediated potentiation resists exposure to pertussis toxin, but is dependent on phospholipase C, and increased phosphatidylinositol (4,5)-bisphosphate hydrolysis. Furthermore, the potentiation of release does not depend on protein kinase C, although it is blocked by the diacylglycerol-binding site antagonist calphostin C. We also found that activation of mGlu7 receptors translocate the active zone protein essential for synaptic vesicle priming, munc13-1, from soluble to particulate fractions. We propose that the mGlu7 receptor can facilitate or inhibit glutamate release through multiple pathways, thereby exerting homeostatic control of presynaptic function.