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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Extracellular domains of alpha-neurexins participate in regulating synaptic transmission by selectively affecting N- and P/Q-type Ca2+ channels.
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Extracellular domains of alpha-neurexins participate in regulating synaptic transmission by selectively affecting N- and P/Q-type Ca2+ channels.

机译：α-神经毒素的胞外域通过选择性影响N型和P / Q型Ca2 +通道参与调节突触传递。

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摘要

Neurexins constitute a large family of highly variable cell-surface molecules that may function in synaptic transmission and/or synapse formation. Each of the three known neurexin genes encodes two major neurexin variants, alpha- and beta-neurexins, that are composed of distinct extracellular domains linked to identical intracellular sequences. Deletions of one, two, or all three alpha-neurexins in mice recently demonstrated their essential role at synapses. In multiple alpha-neurexin knock-outs, neurotransmitter release from excitatory and inhibitory synapses was severely reduced, primarily probably because voltage-dependent Ca2+ channels were impaired. It remained unclear, however, which neurexin variants actually influence exocytosis and Ca2+ channels, which domain of neurexins is required for this function, and which Ca2+-channel subtypes are regulated. Here, we show by electrophysiological recordings that transgenic neurexin 1alpha rescues the release and Ca2+-current phenotypes, whereas transgenic neurexin 1beta has no effect, indicating the importance of the extracellular sequences for the function of neurexins. Because neurexin 1alpha rescued the knock-out phenotype independent of the alpha-neurexin gene deleted, these data are consistent with a redundant function among different alpha-neurexins. In both knock-out and transgenically rescued mice, alpha-neurexins selectively affected the component of neurotransmitter release that depended on activation of N- and P/Q-type Ca2+ channels, but left L-type Ca2+ channels unscathed. Our findings indicate that alpha-neurexins represent organizer molecules in neurotransmission that regulate N- and P/Q-type Ca2+ channels, constituting an essential role at synapses that critically involves the extracellular domains of neurexins.
机译：神经毒素构成大家族的高度可变的细胞表面分子，其可以在突触传递和/或突触形成中起作用。三种已知的神经毒素基因中的每一个均编码两种主要的神经毒素变体，即α-和β-神经毒素，它们由连接至相同细胞内序列的不同细胞外域组成。最近在小鼠中缺失一种，两种或所有三种α-神经毒素表明它们在突触中起着至关重要的作用。在多个α-神经毒素基因敲除中，兴奋性和抑制性突触中神经递质的释放严重减少，主要可能是因为依赖电压的Ca2 +通道受损。但是，尚不清楚哪些神经毒素变体实际上影响胞吐作用和Ca2 +通道，该功能需要哪个神经毒素域，以及哪些Ca2 +通道亚型受到调节。在这里，我们通过电生理学记录表明，转基因神经毒素1alpha拯救了释放和Ca2 +-当前表型，而转基因神经毒素1beta没有作用，表明细胞外序列对于神经毒素功能的重要性。因为神经毒素1alpha拯救了独立于缺失的α-神经毒素基因的敲除表型，所以这些数据与不同的α-神经毒素之间的冗余功能一致。在敲除和转基因挽救的小鼠中，α-神经毒素选择性影响神经递质释放的成分，这取决于N和P / Q型Ca2 +通道的激活，但使L型Ca2 +通道不受损害。我们的发现表明，α-神经毒素代表神经传递中的调节器分子，调节N型和P / Q型Ca2 +通道，在关键涉及神经毒素的胞外域的突触中起重要作用。

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