Retrograde semaphorin-plexin signalling drives homeostatic synaptic plasticity.

Retrograde semaphorin-plexin signalling drives homeostatic synaptic plasticity.
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DOI:
10.1038/nature24017
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发表时间:
2017-10-05
期刊:
影响因子:
64.8
通讯作者:
Davis GW
Davis GW
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Orr BO;Fetter RD;Davis GW

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稳态信号系统确保稳定,但灵活的神经活动和动物行为。为了建立与神经系统疾病的原因和进展的明确联系,确定神经元稳态信号传导的潜在分子机制将是至关重要的。突触前稳态可塑性(PHP)是神经元稳态信号的一种保守形式,在从果蝇到人类的生物体中观察到。在这里,我们证明,Semaphorin 2b(Sema 2b)是靶源性信号,作用于突触前丛蛋白B(PlexB)受体介导的突触前神经递质释放在果蝇神经肌肉接头的逆行,稳态控制。Sema 2b-PlexB信号通过胞质蛋白Mical和突触前肌动蛋白的氧化还原酶依赖性控制来调节PHP的表达。在神经发育过程中,脑信号蛋白-丛蛋白信号指导轴突导向和神经元形态发生。然而,脑信号蛋白和丛状蛋白也在成人大脑中表达。在这里,我们证明,脑信号蛋白丛蛋白信号控制突触前神经递质的释放。我们认为,Sema 2b-PlexB信号是一个重要的平台,在整个生命的突触传递的稳定。
Homeostatic signaling systems ensure stable, yet flexible neural activity and animal behavior. Defining the underlying molecular mechanisms of neuronal homeostatic signaling will be essential in order to establish clear connections to the causes and progression of neurological disease. Presynaptic homeostatic plasticity (PHP) is a conserved form of neuronal homeostatic signaling, observed in organisms ranging from Drosophila to human. Here, we demonstrate that Semaphorin2b (Sema2b) is target-derived signal that acts upon presynaptic PlexinB (PlexB) receptors to mediate the retrograde, homeostatic control of presynaptic neurotransmitter release at the Drosophila neuromuscular junction. Sema2b-PlexB signaling regulates the expression of PHP via the cytoplasmic protein Mical and the oxoreductase-dependent control of presynaptic actin. During neural development, Semaphorin-Plexin signaling instructs axon guidance and neuronal morphogenesis. Yet, Semaphorins and Plexins are also expressed in the adult brain. Here we demonstrate that Semaphorin-Plexin signaling controls presynaptic neurotransmitter release. We propose that Sema2b-PlexB signaling is an essential platform for the stabilization of synaptic transmission throughout life.
Mical Link将信号量与F-肌动蛋白拆卸。
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