活动诱发和自发的突触融合孔开放。
Activity-evoked and spontaneous opening of synaptic fusion pores.
机构信息
Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261.
Department of Neurobiology and Behavior, Cornell University, Ithaca, NY 14853.
出版信息
Proc Natl Acad Sci U S A. 2019 Aug 20;116(34):17039-17044. doi: 10.1073/pnas.1905322116. Epub 2019 Aug 5.
Synaptic release of neuropeptides packaged in dense-core vesicles (DCVs) regulates synapses, circuits, and behaviors including feeding, sleeping, and pain perception. Here, synaptic DCV fusion pore openings are imaged without interference from cotransmitting small synaptic vesicles (SSVs) with the use of a fluorogen-activating protein (FAP). Activity-evoked kiss and run exocytosis opens synaptic DCV fusion pores away from active zones that readily conduct molecules larger than most native neuropeptides (i.e., molecular weight [MW] up to, at least, 4.5 kDa). Remarkably, these synaptic fusion pores also open spontaneously in the absence of stimulation and extracellular Ca SNARE perturbations demonstrate different mechanisms for activity-evoked and spontaneous fusion pore openings with the latter sharing features of spontaneous small molecule transmitter release by active zone-associated SSVs. Fusion pore opening at resting synapses provides a mechanism for activity-independent peptidergic transmission.
神经肽在致密核心囊泡（DCVs）中被包装，并通过突触释放来调节突触、回路和行为，包括进食、睡眠和疼痛感知。在这里，利用荧光蛋白激活蛋白（FAP），可以在不干扰共转运的小突触囊泡（SSVs）的情况下，对突触 DCV 融合孔开口进行成像。活性诱导的 kiss-and-run 胞吐作用使突触 DCV 融合孔远离活性区打开，而活性区很容易传导比大多数天然神经肽（即分子量 [MW] 至少高达 4.5kDa）更大的分子。值得注意的是，这些突触融合孔在没有刺激和细胞外 Ca SNARE 扰动的情况下也会自发打开，表明活性诱导和自发融合孔开口的机制不同，后者具有与活性区相关的 SSV 自发释放小分子递质的特征。在静息突触处打开融合孔为非活动依赖性肽传递提供了一种机制。
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