Differential Co-release of Two Neurotransmitters from a Vesicle Fusion Pore in Mammalian Adrenal Chromaffin Cells

Zhang, Quanfeng; Liu, Bin; Wu, Qihui; Liu, Bing; Li, Yinglin; Sun, Shuang; Wang, Yuan; Wu, Xi; Chai, Zuying; Jiang, Xiaohan; Liu, Xiaoyao; Hu, Meiru; Wang, Yeshi; Yang, Yunting; Wang, Li; Kang, Xinjiang; Xiong, Yong; Zhou, Yang; Chen, Xiaoke; Zheng, Lianghong; Zhang, Bo; Wang, Changhe; Zhu, Feipeng; Zhou, Zhuan

doi:10.1016/j.neuron.2019.01.031

Cited by 30 publications

(55 citation statements)

References 65 publications

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“…Using this approach, we demonstrate that cells without Syt-7 release cargos at significantly faster rates than WT cells expressing a full complement of synaptotagmins. Consistent with data from overexpression studies (12,13), this suggests that endogenous Syt-7 constrains rather than accelerates fusion pore expansion (11).…”

Section: Introductionsupporting

confidence: 81%

“…cordingly, vesicle cargos in Syt-7-bearing vesicles were discharged with slower kinetics than those associated with Syt-1-bearing vesicles (32). A recent study by Zhuan Zhou and colleagues posits an alternative scenario, where Syt-7 promotes rather than inhibits fusion pore expansion (11). Here, we used two distinct experimental preparations to address this issue, including primary mouse chromaffin cells lacking Syt-7 and a reconstituted single vesicle fusion assay employing vesicles only expressing one synaptotagmin isoform at a time.…”

Section: Discussionmentioning

confidence: 99%

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Synaptotagmin-7 endows a population of chromaffin cell vesicles with enhanced calcium sensing and delayed content release properties

Bendahmane

Kreutzberger

Chapman-Morales

et al. 2019

Preprint

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Synaptotagmin-7 (Syt-7) is one of two major calcium sensors for exocytosis in adrenal chromaffin cells, the other being synaptotagmin-1 (Syt-1). Despite its undoubted importance, questions remain as to the functional and physiological role of Syt-7 in secretion. We examined this issue using two distinct preparations -mouse chromaffin cells lacking endogenous Syt-7 (KO cells) and a reconstituted system employing cell-derived vesicles expressing either Syt-7 or Syt-1. First, we report using immunofluorescence that Syt-7 exhibits a punctate intracellular distribution consistent with its sorting to organelles, including dense core vesicles. We also find that the likelihood of vesicle fusion in KO cells is markedly lower than in WT cells. When fusion does occur, cargoes are discharged more rapidly when only Syt-1 is available to facilitate release. A distinctive characteristic of KO cells is that secretion runs down after prolonged cholinergic stimulation. In contrast, exocytosis persists in WT cells even with extended exposure to acetylcholine, suggesting a key role for Syt-7 in sustaining the secretory response. To determine the extent to which the aforementioned results are attributable purely to Syt-7, vesicles expressing only Syt-7 or Syt-1 were triggered to fuse on planar supported bilayers bearing plasma membrane SNARE proteins. Here, as in cells, Syt-7 confers substantially greater calcium sensitivity to vesicle fusion than Syt-1 and slows the rate at which cargos are released. Overall, this study demonstrates that by virtue of its high affinity for calcium, Syt-7 plays a central role in regulating secretory output from adrenal chromaffin cells. synaptotagmin | chromaffin cell | exocytosis | granule Correspondence: arunanan@umich.edu Taken together, our data highlight clear functional distinc-Bendahmane et al. | bioRχiv | July 16, 2019 | 1-5

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Section: Introductionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Synaptotagmin-7 endows a population of chromaffin cell vesicles with enhanced calcium sensing and delayed content release properties

Bendahmane

Kreutzberger

Chapman-Morales

et al. 2019

Preprint

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“…S2A-B), which in the presence of raised pre-stimulation [Ca 2+ ] stimulates priming of vesicles beyond WT levels, moving vesicles that normally prime and fuse during the sustained component into the RRP and SRP. Recently, it was reported that kiss-and-run fusion events are upregulated in the Syt-7 KO (Zhang et al, 2019), but see (Segovia et al, 2010).…”

Section: Syt-7 Promotes Ca 2+ -Dependent Priming Of Slow and Fast Relmentioning

confidence: 99%

Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca²⁺-dependent priming

Tawfik

Martins

Houy

et al. 2020

Preprint

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The functional consequences of the co-expression of synaptotagmin-1 and synaptotagmin-7 are unclear. We show that when present separately, synaptotagmin-1 and synaptotagmin-7 act as standalone fast and slow Ca2+-sensors for vesicle fusion in mouse chromaffin cells. When present together, synaptotagmin-7 stimulates Ca2+-dependent vesicle priming and inhibits depriming. The priming effect of Synaptotagmin-7 extends to the Readily Releasable Pool, whose fusion is executed by synaptotagmin-1, indicating synergistic action of the two Ca2+-sensors, although they are only partially colocalized. Synaptotagmin-7 promotes ubMunc13-2-dependent priming and the absence of synaptotagmin-7 renders phorbolesters less effective in stimulating priming, although synaptotagmin-7 independent priming is also observed. Morphologically, synaptotagmin-7 places vesicles in close membrane apposition (< 6 nm); in its absence vesicles accumulate out of reach of the fusion complex (20-40 nm). We suggest that a synaptotagmin-7-dependent movement toward the membrane is involved in Munc13-2/phorbolester/Ca2+-dependent priming and sets the stage for fast and slow exocytosis triggering.

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“…At post-synaptic targets, the release of two transmitters can enhance the strength of the same signal and/or convey unique signals through spatially-restricted receptor expression and second messenger cascades [7,14]. While recent studies have provided insight into these phenomena at the cellular level [11,12,15,16], the behavioral relevance of co-transmission in normal as well as pathological conditions is an area of considerable complexity and interest.…”

Section: Introductionmentioning

confidence: 99%

Octopamine neuron dependent aggression requires dVGLUT from dual-transmitting neurons

et al. 2020

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Neuromodulators such as monoamines are often expressed in neurons that also release at least one fast-acting neurotransmitter. The release of a combination of transmitters provides both "classical" and "modulatory" signals that could produce diverse and/or complementary effects in associated circuits. Here, we establish that the majority of Drosophila octopamine (OA) neurons are also glutamatergic and identify the individual contributions of each neurotransmitter on sex-specific behaviors. Males without OA display low levels of aggression and high levels of inter-male courtship. Males deficient for dVGLUT solely in OA-glutamate neurons (OGNs) also exhibit a reduction in aggression, but without a concurrent increase in inter-male courtship. Within OGNs, a portion of VMAT and dVGLUT puncta differ in localization suggesting spatial differences in OA signaling. Our findings establish a previously undetermined role for dVGLUT in OA neurons and suggests that glutamate uncouples aggression from OA-dependent courtship-related behavior. These results indicate that dual neurotransmission can increase the efficacy of individual neurotransmitters while maintaining unique functions within a multi-functional social behavior neuronal network.

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Differential Co-release of Two Neurotransmitters from a Vesicle Fusion Pore in Mammalian Adrenal Chromaffin Cells

Cited by 30 publications

References 65 publications

Synaptotagmin-7 endows a population of chromaffin cell vesicles with enhanced calcium sensing and delayed content release properties

Synaptotagmin-7 endows a population of chromaffin cell vesicles with enhanced calcium sensing and delayed content release properties

Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca²⁺-dependent priming

Octopamine neuron dependent aggression requires dVGLUT from dual-transmitting neurons

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Differential Co-release of Two Neurotransmitters from a Vesicle Fusion Pore in Mammalian Adrenal Chromaffin Cells

Cited by 30 publications

References 65 publications

Synaptotagmin-7 endows a population of chromaffin cell vesicles with enhanced calcium sensing and delayed content release properties

Synaptotagmin-7 endows a population of chromaffin cell vesicles with enhanced calcium sensing and delayed content release properties

Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming

Octopamine neuron dependent aggression requires dVGLUT from dual-transmitting neurons

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Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca²⁺-dependent priming