Fusion pores and their control of neurotransmitter and hormone release

Chang, Chieh; Chiang, Chung-Wei; Jackson, Meyer B.

doi:10.1085/jgp.201611724

Cited by 80 publications

(96 citation statements)

References 150 publications

(268 reference statements)

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“…; Chang et al . ), no significant change in the amplitude of foot signals in SphK1 KO cells indicates that S1P may not be part of fusion pore structure but is rather important for modulating the kinetics of fusion pore expansion.…”

Section: Discussionmentioning

confidence: 90%

“…The fusion pore may be composed by both proteins and lipids (Bao et al 2016;Sharma and Lindau 2016). However, since it is suggested any changes in foot amplitude of amperometrical spikes may be related to fusion pore composition (Wang et al 2001;Segovia et al 2010;Fang et al 2015;Chang et al 2017), no significant change in the amplitude of foot signals in SphK1 KO cells indicates that S1P may not be part of fusion pore structure but is rather important for modulating the kinetics of fusion pore expansion.…”

Section: S1p Is Not Critical For the Quantal Sizementioning

confidence: 99%

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Extracellular and intracellular sphingosine‐1‐phosphate distinctly regulates exocytosis in chromaffin cells

Jiang

Delaney

Zanin

et al. 2019

Journal of Neurochemistry

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Sphingosine‐1‐phosphate (S1P) is an essential bioactive sphingosine lipid involved in many neurological disorders. Sphingosine kinase 1 (SphK1), a key enzyme for S1P production, is concentrated in presynaptic terminals. However, the role of S1P/SphK1 signaling in exocytosis remains elusive. By detecting catecholamine release from single vesicles in chromaffin cells, we show that a dominant negative SphK1 (SphK1DN) reduces the number of amperometric spikes and increases the duration of foot, which reflects release through a fusion pore, implying critical roles for S1P in regulating the rate of exocytosis and fusion pore expansion. Similar phenotypes were observed in chromaffin cells obtained from SphK1 knockout mice compared to those from wild‐type mice. In addition, extracellular S1P treatment increased the number of amperometric spikes, and this increase, in turn, was inhibited by a selective S1P3 receptor blocker, suggesting extracellular S1P may regulate the rate of exocytosis via activation of S1P3. Furthermore, intracellular S1P application induced a decrease in foot duration of amperometric spikes in control cells, indicating intracellular S1P may regulate fusion pore expansion during exocytosis. Taken together, our study represents the first demonstration that S1P regulates exocytosis through distinct mechanisms: extracellular S1P may modulate the rate of exocytosis via activation of S1P receptors while intracellular S1P may directly control fusion pore expansion during exocytosis. Open science badges This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

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Section: Discussionmentioning

confidence: 90%

Section: S1p Is Not Critical For the Quantal Sizementioning

confidence: 99%

Extracellular and intracellular sphingosine‐1‐phosphate distinctly regulates exocytosis in chromaffin cells

Jiang

Delaney

Zanin

et al. 2019

Journal of Neurochemistry

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“…Alternatively, loss of SERT might favor partial rather than full release of the vesicular content. The properties and stability of the initial fusion pore that forms between the vesicle and extracellular space to allow efflux of transmitters can be regulated 117, 118 . This can result in transient fusion events (sometimes referred to as “kiss-and-run” exocytosis) that release only some of the vesicle cargo.…”

Section: Sert / 5-ht Might Modulate the Late Steps Of Exocytosismentioning

confidence: 99%

Serotonin and Serotonin Transporters in the Adrenal Medulla: A Potential Hub for Modulation of the Sympathetic Stress Response

Brindley

Bauer

Blakely

et al. 2017

ACS Chem. Neurosci.

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Serotonin (5-HT) is an important neurotransmitter in the central nervous system where it modulates circuits involved in mood, cognition, movement, arousal, and autonomic function. The 5-HT transporter (SERT; SLC6A4) is a key regulator of 5-HT signaling, and genetic variations in SERT are associated with various disorders including depression, anxiety, and autism. This review focuses on the role of SERT in the sympathetic nervous system. Autonomic / sympathetic dysfunction is evident in patients with depression, anxiety, and other diseases linked to serotonergic signaling. Experimentally, loss of SERT function (SERT knockout mice or chronic pharmacological block) has been reported to augment the sympathetic stress response. Alterations to serotonergic signaling in the CNS and thus central drive to the peripheral sympathetic nervous system are presumed to underlie this augmentation. Although less widely recognized, SERT is robustly expressed in chromaffin cells of the adrenal medulla, the neuroendocrine arm of the sympathetic nervous system. Adrenal chromaffin cells do not synthesize 5-HT but accumulate small amounts by SERT-mediated uptake. Recent evidence demonstrated that 5-HT1A receptors inhibit catecholamine secretion from adrenal chromaffin cells via an atypical mechanism that does not involve modulation of cellular excitability or voltage-gated Ca2+ channels. This raises the possibility that the adrenal medulla is a previously unrecognized peripheral hub for serotonergic control of the sympathetic stress response. As a framework for future investigation, a model is proposed in which stress-evoked adrenal catecholamine secretion is fine-tuned by SERT-modulated autocrine 5-HT signaling.

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“…Mutations of different residues of synaptotagmin or lengthening of the Syt molecule may retard or shorten the amperometric foot . We will not deal in detail here with all this set of experimental data, for a review see .…”

Section: Fusion Pore Regulation In Chromaffin Granulesmentioning

confidence: 99%

Phases of the exocytotic fusion pore

et al. 2018

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Membrane fusion and fission are fundamental processes in living organisms. Membrane fusion occurs through the formation of a fusion pore, which is the structure that connects two lipid membranes during their fusion. Fusion pores can form spontaneously, but cells endow themselves with a set of proteins that make the process of fusion faster and regulatable. The fusion pore starts with a narrow diameter and dilates relatively slowly; it may fluctuate in size or can even close completely, producing a transient vesicle fusion (kiss-and-run), or can finally expand abruptly to release all vesicle contents. A set of proteins control the formation, dilation, and eventual closure of the fusion pore and, therefore, the velocity at which the contents of secretory vesicles are released to the extracellular medium. Thus, the regulation of fusion pore expansion or closure is key to regulate the release of neurotransmitters and hormones. Here, we review the phases of the fusion pore and discuss the implications in the modes of exocytosis.

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Fusion pores and their control of neurotransmitter and hormone release

Abstract: Chang et al. review fusion pore structure and dynamics and discuss the implications for hormone and neurotransmitter release

Cited by 80 publications

References 150 publications

Extracellular and intracellular sphingosine‐1‐phosphate distinctly regulates exocytosis in chromaffin cells

Extracellular and intracellular sphingosine‐1‐phosphate distinctly regulates exocytosis in chromaffin cells

Serotonin and Serotonin Transporters in the Adrenal Medulla: A Potential Hub for Modulation of the Sympathetic Stress Response

Phases of the exocytotic fusion pore

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