Regulation of presynaptic CaV2.1 channels by Ca2+ sensor proteins mediates short-term synaptic plasticity
Regulation of presynaptic CaV2.1 channels by Ca2+ sensor proteins mediates short-term synaptic plasticity
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DOI：
10.1016/j.neuron.2007.11.036
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发表时间：
2008-01-24
期刊：
影响因子：
16.2
通讯作者：
Catterall, William A.
中科院分区：
文献类型：
--
作者：
Mochida, Sumiko;Few, Alexandra P.;Catterall, William A.
短期突触可塑性塑造了突触后对脉冲爆发的反应，对神经元中的信息编码至关重要，但分子机制尚不清楚。在这里，我们表明，神经元钙传感器蛋白（CaS）介导的突触前Ca（v）2.1通道的活动依赖性调制诱导突触可塑性在培养的上级颈神经节（SCG）神经元。C端IQ样基序的突变阻断P/Q型Ca 2+电流的Ca 2（+）/CaS依赖性易化，显著降低突触传递的易化。删除附近的钙调素结合结构域，抑制CaS依赖性失活，大大减少突触传递的抑郁症。这些结果表明，突触前末梢中的残余Ca 2+可以通过Ca（v）2.1通道的CaS依赖性调节作用，诱导短时程突触易化和快速突触抑制。因此，突触前Ca（v）2.1通道的CaS蛋白的活动依赖性调节可能是神经系统中短期突触可塑性和信息处理的主要决定因素。
Short-term synaptic plasticity shapes the postsynaptic response to bursts of impulses and is crucial for encoding information in neurons, but the molecular mechanisms are unknown. Here we show that activity-dependent modulation of presynaptic Ca(v)2.1 channels mediated by neuronal Ca2+ sensor proteins (CaS) induces synaptic plasticity in cultured superior cervical ganglion (SCG) neurons. A mutation of the IQ-like motif in the C terminus that blocks Ca2(+)/CaS-dependent facilitation of the P/Q-type Ca2+ current markedly reduces facilitation of synaptic transmission. Deletion of the nearby calmodulin-binding domain, which inhibits CaS-dependent inactivation, substantially reduces depression of synaptic transmission. These results demonstrate that residual Ca2+ in presynaptic terminals can act through CaS-dependent regulation of Ca(v)2.1 channels to induce short-term synaptic facilitation and rapid synaptic depression. Activity-dependent regulation of presynaptic Ca(v)2.1 channels by CaS proteins may therefore be a primary determinant of short-term synaptic plasticity and information-processing in the nervous system.