Syntaxin Clustering and Optogenetic Control for Synaptic Membrane Fusion

Li, Miaoling; Oh, Teak Jung; Fan, Huaxun; Diao, Jiajie; Zhang, Kai

doi:10.1016/j.jmb.2020.07.005

Cited by 8 publications

(7 citation statements)

References 119 publications

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“…The conversion between the LA and HA states would then be regulated by membrane trafficking of Sx1A. In support of this hypothesis, it was demonstrated that Sx1A forms dynamic clusters (Bademosi et al, 2017;Li et al, 2020), which regulate spontaneous transmission (Khuong et al, 2013). We favor the hypothesis that the formation of Sx1A clusters generates the hot spots of spontaneous transmission and that this process is enhanced by Cpx dispersion from these hot spots, promoting SNARE zippering.…”

Section: Discussionmentioning

confidence: 59%

Stochastic Properties of Spontaneous Synaptic Transmission at Individual Active Zones

Astacio¹,

Vasin

Bykhovskaia

2021

J. Neurosci.

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Using postsynaptically tethered calcium sensor GCaMP, we investigated spontaneous synaptic transmission at individual active zones (AZs) at the Drosophila (both sexes) neuromuscular junction. Optical monitoring of GCaMP events coupled with focal electrical recordings of synaptic currents revealed "hot spots" of spontaneous transmission, which corresponded to transient states of elevated activity at selected AZs. The elevated spontaneous activity had two temporal components, one at a timescale of minutes and the other at a subsecond timescale. We developed a three-state model of AZ preparedness for spontaneous transmission and performed Monte Carlo simulations of the release process, which produced an accurate quantitative description of the variability and time course of spontaneous transmission at individual AZs. To investigate the mechanisms of elevated activity, we first focused on the protein complexin, which binds the SNARE protein complex and serves to clamp spontaneous fusion. Overexpression of Drosophila complexin largely abolished the high-activity states of AZs, while complexin deletion drastically promoted it. A mutation in the SNARE protein Syntaxin-1A had an effect similar to complexin deficiency, promoting the high-activity state. We next tested how presynaptic Ca 21 transients affect the states of elevated activity at individual AZs. We either blocked or promoted Ca 21 influx pharmacologically, and also promoted Ca 21 release from internal stores. These experiments coupled with computations revealed that Ca 21 transients can trigger bursts of spontaneous events from individual AZs or AZ clusters at a subsecond timescale. Together, our results demonstrated that spontaneous transmission is highly heterogeneous, with transient hot spots being regulated by the SNARE machinery and Ca 21 .

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Section: Discussionmentioning

confidence: 59%

Stochastic Properties of Spontaneous Synaptic Transmission at Individual Active Zones

Astacio¹,

Vasin

Bykhovskaia

2021

J. Neurosci.

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“…In the dorsal and ventral horns, as well as along the pericentral canal, NHE6/Y KO animals showed enhanced microglial and astrocytic immunoreactivity, indicating that exercise training may increase the levels of SLC9A6/NHE6 to decrease the sensory impairments after SCI. The current study found that exercise training is effective in alleviating the neuropathic pain caused by partial SCI in rats ( Li et al, 2020a ; Li et al, 2020b ; Li et al, 2020c ). In this study, it was discovered that SLC9A6 was elevated.…”

Section: Discussionmentioning

confidence: 56%

“…S1 ). In previous studies, SCI-induced microglial activation and successive release of inflammatory factors i.e., tumor necrosis factor (TNF), interferon (INF), and interleukin (IL) have been shown to cause direct death of neurons however induction in vascular endothelial cells for the expression of a range of chemotaxis and cell adhesion molecules ( Li et al, 2020a ; Li et al, 2020b ; Li et al, 2020c ; Orr & Gensel, 2018 ). In our study, within three weeks of post-SCI, the levels of mRNA expressions of IL-6, TNF-α, and IL-1β were increased.…”

Section: Resultsmentioning

confidence: 99%

“…Syntaxin-7(Stx7) is a syntaxin family membrane receptor involved in vesicle transport ( Wang, Frelin & Pevsner, 1997 ). Syntaxin is involved in vesicle docking and fusion, both of which are required for neurotransmitter release ( Hammarlund et al, 2007 ; Li et al, 2020a ; Li et al, 2020b ; Li et al, 2020c ). Ying et al (2012) reported that spinal cord can decrease the levels of Syntaxin-3 (Stx3) after traumatic brain injury, which affects membrane homeostasis.…”

Section: Discussionmentioning

confidence: 99%

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LncRNA/miRNA/mRNA ceRNA network analysis in spinal cord injury rat with physical exercise therapy

Wang

et al. 2022

PeerJ

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Noncoding RNAs have been implicated in the pathophysiology of spinal cord injury (SCI), including cell death, glial scar formation, axonal collapse and demyelination, and inflammation. The evidence suggests that exercise therapy is just as effective as medical treatment in SCI. However, studies of competing endogenous RNA (ceRNA)-mediated regulation mechanisms in the therapy of SCI with exercise are rare. The focus of this research was to investigate the effect of exercise therapy on the expression levels of long noncoding RNA (lncRNA), microRNA (miRNA), and mRNA in rats with SCI. The RNA-seq technology has been used to examine the differentially expressed circRNAs (DECs), lncRNAs (DELs), miRNAs (DEMs), and genes (DEGs) between SCI and exercise therapy rats. The ceRNA network was established using interactions between miRNAs and mRNAs, as well as between miRNAs and lncRNAs/circRNAs. The Database for Annotation, Visualization, and Integrated Discovery was used to anticipate the underlying functions of mRNAs. Our current study identified 76 DELs, 33 DEMs, and 30 DEGs between groups of SCI rats and exercise therapy rats. Subsequently, these newly discovered ceRNA interaction axes could be important targets for the exercise treatment of SCI.

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“…The SNARE complex is considered to be a bridge between intracellular vesicles and the plasma membrane in addition to being a core fusion element (Shi et al, 2012;Fang and Lindau, 2014;Brunger et al, 2015;Tian et al, 2019). Binding and assembly of SNARE proteins are sufficient to drive the fusion of SVs (McNew et al, 2000;Li et al, 2020); however, the fast kinetics of membrane fusion, which occurs in the order of milliseconds, requires the precise coordination of SNAREs and auxiliary synaptic proteins (Weber et al, 1998;Rizo and Rosenmund, 2008;Zhou et al, 2017;Neher and Brose, 2018;Salpietro et al, 2019;Tian et al, 2019;Li et al, 2020;Sauvola and Littleton, 2021). The key regulatory components include chaperones Sec1/Munc18 (SM) protein family, the primary Ca 2+ sensor synaptotagmin (SYT), complexins (CPX) protein, and N-ethylmaleimide sensitive factor (NSF) (Weber et al, 1998;Melia et al, 2002;Rizo and Rosenmund, 2008;Südhof and Rothman, 2009;Diao et al, 2011;He et al, 2017;Zhou et al, 2017;Salpietro et al, 2019;Li et al, 2020;Wang C. et al, 2020;Wang X. et al, 2020).…”

Section: The Role Of Vampin Membrane Fusionmentioning

confidence: 99%

The function of VAMP2 in mediating membrane fusion: An overview

Chong

Jiang²,

Yang³

et al. 2022

Front. Mol. Neurosci.

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Vesicle-associated membrane protein 2 (VAMP2, also known as synaptobrevin-2), encoded by VAMP2 in humans, is a key component of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. VAMP2 combined with syntaxin-1A (SYX-1A) and synaptosome-associated protein 25 (SNAP-25) produces a force that induces the formation of fusion pores, thereby mediating the fusion of synaptic vesicles and the release of neurotransmitters. VAMP2 is largely unstructured in the absence of interaction partners. Upon interaction with other SNAREs, the structure of VAMP2 stabilizes, resulting in the formation of four structural domains. In this review, we highlight the current knowledge of the roles of the VAMP2 domains and the interaction between VAMP2 and various fusion-related proteins in the presynaptic cytoplasm during the fusion process. Our summary will contribute to a better understanding of the roles of the VAMP2 protein in membrane fusion.

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Syntaxin Clustering and Optogenetic Control for Synaptic Membrane Fusion

Cited by 8 publications

References 119 publications

Stochastic Properties of Spontaneous Synaptic Transmission at Individual Active Zones

Stochastic Properties of Spontaneous Synaptic Transmission at Individual Active Zones

LncRNA/miRNA/mRNA ceRNA network analysis in spinal cord injury rat with physical exercise therapy

The function of VAMP2 in mediating membrane fusion: An overview

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