Interdependence of PKC-Dependent and PKC-Independent Pathways for Presynaptic Plasticity
Interdependence of PKC-Dependent and PKC-Independent Pathways for Presynaptic Plasticity
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DOI：
10.1016/j.neuron.2007.04.001
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发表时间：
2007-04
期刊：
影响因子：
16.2
通讯作者：
Keimpe D. Wierda;R. Toonen;H. Wit;A. Brussaard;M. Verhage
中科院分区：
文献类型：
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作者：
Keimpe D. Wierda;R. Toonen;H. Wit;A. Brussaard;M. Verhage
甘油二酯（DAG）是突触传递的重要内源性调节剂。最近的研究提出了两个明显不相容的途径，通过蛋白激酶C（PKC）和通过Munc 13。在这里，我们展示了这两种途径是如何融合的。首先，我们证实，DAG类似物确实继续增强PKC抑制后的传输（Munc 13途径），但只有在神经元，以前经历过DAG类似物，PKC抑制开始之前。第二，我们通过表达PKC不敏感的Munc 18 -1突变体inmunc 18 - 1 null突变体神经元来鉴定一个重要的PKC通路。该突变体支持基本的传输，但不支持DAG诱导的增强和囊泡再分布。此外，突触抑制增加，但不是由高渗溶液引起的Ca 2+非依赖性释放。这些数据表明，激活PKC依赖性和非依赖性途径（通过Munc 13）是必需的DAG诱导的增强。Munc 18 -1是PKC通路中的重要下游靶点。这条通路对于突触前可塑性具有普遍的重要性。
Diacylglycerol (DAG) is a prominent endogenous modulator of synaptic transmission. Recent studies proposed two apparently incompatible pathways, via protein kinase C (PKC) and via Munc13. Here we show how these two pathways converge. First, we confirm that DAG analogs indeed continue to potentiate transmission after PKC inhibition (the Munc13 pathway), but only in neurons that previously experienced DAG analogs, before PKC inhibition started. Second, we identify an essential PKC pathway by expressing a PKC-insensitive Munc18-1 mutant inmunc18-1null mutant neurons. This mutant supported basic transmission, but not DAG-induced potentiation and vesicle redistribution. Moreover, synaptic depression was increased, but not Ca2+-independent release evoked by hypertonic solutions. These data show that activation of both PKC-dependent and -independent pathways (via Munc13) are required for DAG-induced potentiation. Munc18-1 is an essential downstream target in the PKC pathway. This pathway is of general importance for presynaptic plasticity.