Departments of Psychiatry, Neurology and Pharmacology, Columbia University Medical Center, New York State Psychiatric Institute.
Departments of Neurology and Physiology, Graduate Programs in Cell Biology, Biomedical Sciences and Neuroscience, UCSF School of Medicine.
J Neurochem. 2019 Sep;150(5):475-486. doi: 10.1111/jnc.14810. Epub 2019 Jul 28.
The protein α-synuclein has a central role in the pathogenesis of Parkinson's disease (PD). In this review, we discuss recent results concerning its primary function, which appears to be on cell membranes. The pre-synaptic location of synuclein has suggested a role in neurotransmitter release and it apparently associates with synaptic vesicles because of their high curvature. Indeed, synuclein over-expression inhibits synaptic vesicle exocytosis. However, loss of synuclein has not yet been shown to have a major effect on synaptic transmission. Consistent with work showing that synuclein can promote as well as sense membrane curvature, recent analysis of synuclein triple knockout mice now shows that synuclein accelerates dilation of the exocytic fusion pore. This form of regulation affects primarily the release of slowly discharged lumenal cargo such as neural peptides, but presumably also contributes to maintenance of the release site. This article is part of the Special Issue "Synuclein".
蛋白α-突触核蛋白在帕金森病 (PD) 的发病机制中起核心作用。在这篇综述中，我们讨论了其主要功能的最新结果，其主要功能似乎在细胞膜上。突触核蛋白的前突触位置提示其在神经递质释放中的作用，并且由于其高曲率，它显然与突触小泡相关联。事实上，突触核蛋白的过度表达抑制突触小泡胞吐作用。然而，突触核蛋白的缺失尚未被证明对突触传递有重大影响。与表明突触核蛋白可以促进和感知膜曲率的工作一致，最近对突触核蛋白三重敲除小鼠的分析表明，突触核蛋白加速了胞吐融合孔的扩张。这种调节形式主要影响缓慢释放腔内容物（如神经肽）的释放，但推测也有助于释放部位的维持。本文是“突触核蛋白”特刊的一部分。
