Synapse type-independent degradation of the endocannabinoid 2-arachidonoylglycerol after retrograde synaptic suppression
Synapse type-independent degradation of the endocannabinoid 2-arachidonoylglycerol after retrograde synaptic suppression
复制标题
逆行突触抑制后内源性大麻素 2-花生四烯酰甘油的突触类型独立降解
DOI：
10.1073/pnas.1204404109
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Tanimura A
中科院分区：
文献类型：
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作者：
渡部綾子;瀬谷司;松本美佐子;Tanimura A
内源性大麻素2-花生四烯基甘油(2-AG)介导了突触的逆行抑制。虽然2-氨基酚的产生机制已经被很好地描述，但2-氨基酚是如何被降解的还不是很清楚。我们发现2-AG水解酶单酰甘油脂肪酶(MGL)在小脑中的表达是高度异质性的，在平行纤维(PF)终末表达丰富，在Bergman神经胶质(BG)表达弱，在其他突触终末缺乏表达。尽管有这种高度选择性的MGL表达模式，但在小脑MGL表达局限于BG的颗粒细胞特异性MGL基因敲除(MGL-KO)小鼠中，2-AG介导的逆行抑制不仅在PF-Purkinje细胞(PC)突触上显著延长，而且在攀升纤维-PC突触上也显著延长。病毒介导的MGL在全球MGL-KO小鼠的BG中的表达显著缩短了2-AG介导的PF-PC突触的逆行抑制。此外，MGL对终止2-AG信号的作用依赖于富含MGL的PFS到抑制性突触终末的距离。因此，2-AG被存在于PFS和BG中的MGL以突触类型独立的方式降解。目前的研究结果强烈表明，MGL在一定范围的神经组织中调节2-AG信号相当广泛，尽管MGL的表达是异质性的，仅限于神经末梢和星形胶质细胞的一部分。
The endocannabinoid 2-arachidonoylglycerol (2-AG) mediates retrograde synaptic suppression. Although the mechanisms of 2-AG production are well characterized, how 2-AG is degraded is less clearly understood. Here we found that expression of the 2-AG hydrolyzing enzyme monoacylglycerol lipase (MGL) was highly heterogeneous in the cerebellum, being rich within parallel fiber (PF) terminals, weak in Bergman glia (BG), and absent in other synaptic terminals. Despite this highly selective MGL expression pattern, 2-AG–mediated retrograde suppression was significantly prolonged at not only PF-Purkinje cell (PC) synapses but also climbing fiber-PC synapses in granule cell-specific MGL knockout (MGL-KO) mice whose cerebellar MGL expression was confined to the BG. Virus-mediated expression of MGL into the BG of global MGL-KO mice significantly shortened 2-AG–mediated retrograde suppression at PF-PC synapses. Furthermore, contribution of MGL to termination of 2-AG signaling depended on the distance from MGL-rich PFs to inhibitory synaptic terminals. Thus, 2-AG is degraded in a synapse-type independent manner by MGL present in PFs and the BG. The results of the present study strongly suggest that MGL regulates 2-AG signaling rather broadly within a certain range of neural tissue, although MGL expression is heterogeneous and limited to a subset of nerve terminals and astrocytes.