Orr Brian O, Fetter Richard D, Davis Graeme W
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158, USA.
Nature. 2017 Oct 5;550(7674):109-113. doi: 10.1038/nature24017. Epub 2017 Sep 27.
Homeostatic signalling systems ensure stable but flexible neural activity and animal behaviour. Presynaptic homeostatic plasticity is a conserved form of neuronal homeostatic signalling that is observed in organisms ranging from Drosophila to human. Defining the underlying molecular mechanisms of neuronal homeostatic signalling will be essential in order to establish clear connections to the causes and progression of neurological disease. During neural development, semaphorin-plexin signalling instructs axon guidance and neuronal morphogenesis. However, semaphorins and plexins are also expressed in the adult brain. Here we show that semaphorin 2b (Sema2b) is a target-derived signal that acts upon presynaptic plexin B (PlexB) receptors to mediate the retrograde, homeostatic control of presynaptic neurotransmitter release at the neuromuscular junction in Drosophila. Further, we show that Sema2b-PlexB signalling regulates presynaptic homeostatic plasticity through the cytoplasmic protein Mical and the oxoreductase-dependent control of presynaptic actin. We propose that semaphorin-plexin signalling is an essential platform for the stabilization of synaptic transmission throughout the developing and mature nervous system. These findings may be relevant to the aetiology and treatment of diverse neurological and psychiatric diseases that are characterized by altered or inappropriate neural function and behaviour.
稳态信号系统确保神经活动和动物行为稳定且灵活。突触前稳态可塑性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均有观察到。为了明确与神经疾病的病因和进展建立清晰联系，确定神经元稳态信号的潜在分子机制至关重要。在神经发育过程中，信号素 - 丛蛋白信号传导指导轴突导向和神经元形态发生。然而，信号素和丛蛋白在成体大脑中也有表达。在此我们表明，信号素2b（Sema2b）是一种源自靶标的信号，作用于突触前丛蛋白B（PlexB）受体，以介导果蝇神经肌肉接头处突触前神经递质释放的逆行性稳态控制。此外，我们表明Sema2b - PlexB信号传导通过细胞质蛋白Mical和突触前肌动蛋白的氧化还原酶依赖性控制来调节突触前稳态可塑性。我们提出，信号素 - 丛蛋白信号传导是整个发育和成熟神经系统中突触传递稳定的重要平台。这些发现可能与多种以神经功能和行为改变或不适当为特征的神经和精神疾病的病因学及治疗相关。
