Departamento de Bioquímica, Facultad de Veterinaria, Universidad Complutense, Madrid, Spain.
J Neurochem. 2011 Feb;116(4):476-85. doi: 10.1111/j.1471-4159.2010.07134.x. Epub 2011 Jan 19.
We recently showed that prolonged activation of metabotropic glutamate receptor 7 (mGlu7) potentiates glutamate release. This signalling involves phospholipase C activation via a pertussis toxin insensitive G protein and the subsequent hydrolysis of phosphatidylinositol (4,5)-bisphosphate. Release potentiation is independent of protein kinase C activation but it is dependent on the downstream release machinery, as reflected by the concomitant translocation of active zone Munc13-1 protein from the soluble to particulate fractions. Here we show that phorbol ester and mGlu7 receptor-dependent facilitation of neurotransmitter release is not additive, suggesting they share a common signalling mechanism. However, release potentiation is restricted to release sites that express N-type Ca(2+) channels, because phorbol ester and mGlu7 receptor-mediated release potentiation are absent in nerve terminals from mice lacking N-type Ca(2+) channels. In addition, phorbol esters but not mGlu7 receptors potentiate release at nerve terminals with P/Q-type Ca(2+) channels, although only under restricted conditions of Ca(2+) influx. The differential effect of phorbol esters at nerve terminals with either N- or P/Q-type Ca(2+) channels seems to be unrelated to the type Munc13 isoform expressed, and it is more likely dependent on other properties of the release machinery.
我们最近发现，代谢型谷氨酸受体 7（mGlu7）的持续激活可增强谷氨酸释放。这种信号转导涉及通过百日咳毒素不敏感 G 蛋白激活磷脂酶 C，随后水解磷脂酰肌醇（4,5）-二磷酸。释放增强不依赖于蛋白激酶 C 的激活，但依赖于下游释放机制，这反映在活性区 Munc13-1 蛋白从可溶性部分到颗粒部分的同时易位。在这里，我们发现佛波酯和 mGlu7 受体依赖性神经递质释放增强不是加性的，表明它们共享一个共同的信号机制。然而，释放增强仅限于表达 N 型钙（Ca2+）通道的释放位点，因为在缺乏 N 型 Ca2+通道的小鼠神经末梢中，佛波酯和 mGlu7 受体介导的释放增强不存在。此外，佛波酯而非 mGlu7 受体可增强具有 P/Q 型 Ca2+通道的神经末梢的释放，尽管仅在 Ca2+流入的受限条件下。佛波酯在具有 N 型或 P/Q 型 Ca2+通道的神经末梢中的差异作用似乎与表达的 Munc13 同工型无关，更可能取决于释放机制的其他特性。
