The Synaptic Vesicle Glycoprotein 2: Structure, Function, and Disease Relevance

突触小泡 神经科学 生物 神经传递 快照25 突触囊泡循环 神经退行性变 小泡 功能(生物学) 细胞生物学 生物化学 疾病 医学 受体 内科学
作者
Kristen A. Stout,Amy R. Dunn,Carlie Hoffman,Gary W. Miller
出处
期刊:ACS Chemical Neuroscience [American Chemical Society]
卷期号:10 (9): 3927-3938 被引量:85
标识
DOI:10.1021/acschemneuro.9b00351
摘要

The synaptic vesicle glycoprotein 2 (SV2) family is comprised of three paralogues: SV2A, SV2B, and SV2C. In vertebrates, SV2s are 12-transmembrane proteins present on every secretory vesicle, including synaptic vesicles, and are critical to neurotransmission. Structural and functional studies suggest that SV2 proteins may play several roles to promote proper vesicular function. Among these roles are their potential to stabilize the transmitter content of vesicles, to maintain and orient the releasable pool of vesicles, and to regulate vesicular calcium sensitivity to ensure efficient, coordinated release of the transmitter. The SV2 family is highly relevant to human health in a number of ways. First, SV2A plays a role in neuronal excitability and as such is the specific target for the antiepileptic drug levetiracetam. SV2 proteins also act as the target by which potent neurotoxins, particularly botulinum, gain access to neurons and exert their toxicity. Both SV2B and SV2C are increasingly implicated in diseases such as Alzheimer's disease and Parkinson's disease. Interestingly, despite decades of intensive research, their exact function remains elusive. Thus, SV2 proteins are intriguing in their potentially diverse roles within the presynaptic terminal, and several recent developments have enhanced our understanding and appreciation of the protein family. Here, we review the structure and function of SV2 proteins as well as their relevance to disease and therapeutic development.
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