Downregulation of Centaurin gamma1A increases synaptic transmission at Drosophila larval neuromuscular junctions
Downregulation of Centaurin gamma1A increases synaptic transmission at Drosophila larval neuromuscular junctions
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DOI：
10.1111/ejn.12681
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发表时间：
2014-10-01
影响因子：
3.4
通讯作者：
Morimoto, Takako
中科院分区：
文献类型：
--
作者：
Homma, Mizuho;Nagashima, Shun;Morimoto, Takako
突触传递的充分调节对于神经回路的适当功能至关重要。尽管已鉴定出许多参与突触神经传递的分子，但调节神经传递的分子机制尚未完全了解。在这里，我们重点关注半人马座蛋白 gamma1A (CenG1A)，并利用果蝇幼虫神经肌肉接头检查其在突触传递调节中的作用。 CenG1A 是 Centaurin 家族的成员，该家族包含 Pleckstrin 同源物、ADP 核糖基化因子 GTP 酶激活蛋白和锚蛋白重复结构域。由于这些功能域的存在，CenG1A被认为参与突触释放过程；然而，迄今为止尚未发现任何证据。在这项研究中，我们通过在幼虫肌肉细胞中进行细胞内记录，研究了 CenG1A 在突触释放过程中的潜在作用。我们发现 cenG1A 突变体突触前细胞释放的神经递质增强。在突触前或突触后细胞中 CenG1A 功能降低的幼虫中也观察到了这种效应。此外，我们发现抑制突触后肌细胞中的 CenG1A 功能会导致神经递质释放概率增加，而突触前神经元中的 CenG1A 功能抑制会导致神经递质释放概率增加和突触小泡数量增加。这些结果表明 CenG1A 在突触前和突触后位点发挥神经递质释放的负调节作用。我们的研究提供了 CenG1A 在神经肌肉接头正确突触传递中的关键作用的证据。
Adequate regulation of synaptic transmission is critical for appropriate neural circuit functioning. Although a number of molecules involved in synaptic neurotransmission have been identified, the molecular mechanisms regulating neurotransmission are not fully understood. Here, we focused on Centaurin gamma1A (CenG1A) and examined its role in synaptic transmission regulation using Drosophila larval neuromuscular junctions. CenG1A is a member of the Centaurin family, which contains Pleckstrin homology, ADP ribosylation factor GTPase-activating protein, and ankyrin repeat domains. Due to the existence of these functional domains, CenG1A is proposed to be involved in the process of synaptic release; however, no evidence for this has been found to date. In this study, we investigated the potential role for CenG1A in the process of synaptic release by performing intracellular recordings in larval muscle cells. We found that neurotransmitter release from presynaptic cells was enhanced in cenG1A mutants. This effect was also observed in larvae with reduced CenG1A function in either presynaptic or postsynaptic cells. In addition, we revealed that suppressing CenG1A function in postsynaptic muscle cells led to an increase in the probability of neurotransmitter release, whereas its suppression in presynaptic neurons led to an increase in neurotransmitter release probability and an increase in the number of synaptic vesicles. These results suggested that CenG1A functions at both presynaptic and postsynaptic sites as a negative regulator of neurotransmitter release. Our study provided evidence for a key role of CenG1A in proper synaptic transmission at neuromuscular junctions.