Department of Cell Biology & Anatomy, New York Medical College, Valhalla, NY 10595, USA.
Neuropharmacology. 2013 Mar;66:31-9. doi: 10.1016/j.neuropharm.2012.05.004. Epub 2012 May 22.
While postsynaptic ionotropic and metabotropic glutamate receptors have received the lions share of attention in studies of long-term activity-dependent synaptic plasticity, it is becoming clear that presynaptic metabotropic glutamate receptors play critical roles in both short-term and long-term plasticity of vesicular transmitter release, and that they act both at the level of voltage-dependent calcium channels and directly on proteins of the vesicular release machinery. Activation of G protein-coupled receptors can transiently inhibit vesicular release through the release of Gβγ which binds to both voltage-dependent calcium channels to reduce calcium influx, and directly to the C-terminus region of the SNARE protein SNAP-25. Our recent work has revealed that the binding of Gβγ to SNAP-25 is necessary, but not sufficient, to elicit long-term depression (LTD) of vesicular glutamate release, and that the concomitant release of Gα(i) and the second messenger nitric oxide are also necessary steps in the presynaptic LTD cascade. Here, we review the current state of knowledge of the molecular steps mediating short-term and long-term plasticity of vesicular release at glutamatergic synapses, and the many gaps that remain to be addressed. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.
虽然离子型和代谢型谷氨酸受体在后突触在长时程活性依赖突触可塑性的研究中受到了广泛关注，但现在越来越清楚的是，前突触代谢型谷氨酸受体在囊泡递质释放的短期和长期可塑性中都发挥着关键作用，并且它们既作用于电压依赖性钙通道，也直接作用于囊泡释放机制的蛋白。G 蛋白偶联受体的激活可以通过释放 Gβγ来短暂抑制囊泡释放，Gβγ 结合电压依赖性钙通道以减少钙内流，并直接结合 SNARE 蛋白 SNAP-25 的 C 端区域。我们最近的工作表明，Gβγ 与 SNAP-25 的结合对于引发囊泡谷氨酸释放的长时程抑制（LTD）是必要的，但不是充分的，并且 Gα(i)和第二信使一氧化氮的同时释放也是突触 LTD 级联反应中的必要步骤。在这里，我们综述了目前对谷氨酸能突触囊泡释放的短期和长期可塑性的分子步骤的认识，以及仍然存在的许多需要解决的问题。本文是题为“代谢型谷氨酸受体”的特刊的一部分。
