Compound versus multigranular exocytosis in peritoneal mast cells.

Toledo, G. Álvarez de; Fernández, Julio M.

doi:10.1085/jgp.95.3.397

Cited by 130 publications

(130 citation statements)

References 17 publications

(28 reference statements)

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“…insulin secretion in diabetes, mast cell secretion in allergic reactions) [28]. One mode is fusion of secretory granules, either by orderly sequential fusion as in pancreatic acinar cells [13,20] or by prior homotypic fusion leading to compound exocytosis, as in mast cells [35]. Islet beta cells employ fusion of secretory granules [31,36], but to a much lesser extent than other secretory cells.…”

Section: Discussionmentioning

confidence: 99%

Syntaxin-3 regulates newcomer insulin granule exocytosis and compound fusion in pancreatic beta cells

et al. 2012

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Aims/hypothesis The molecular basis of the exocytosis of secretory insulin-containing granules (SGs) during biphasic glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells remains unclear. Syntaxin (SYN)-1A and SYN-4 have been shown to mediate insulin exocytosis. The insulinsecretory function of SYN-3, which is particularly abundant in SGs, is unclear. Methods Mouse pancreatic islets and INS-1 cells were treated with adenovirus carrying Syn-3 (also known as Stx3) or small interfering RNA targeting Syn-3 in order to examine insulin secretion by radioimmunoassay. The localisation and distribution of insulin granules were examined by confocal and electron microscopy. Dynamic single-granule fusion events were assessed using total internal reflection fluorescence microscopy (TIRFM). Results Depletion of endogenous SYN-3 inhibited insulin release. TIRFM showed no change in the number or fusion competence of previously docked SGs but, instead, a marked reduction in the recruitment of newcomer SGs and their subsequent exocytotic fusion during biphasic GSIS. Conversely, overexpression of Syn-3 enhanced both phases of GSIS, owing to the increase in newcomer SGs and, remarkably, to increased SG-SG fusion, which was confirmed by electron microscopy. Conclusions/interpretation In insulin secretion, SYN-3 plays a role in the mediation of newcomer SG exocytosis and SG-SG fusion that contributes to biphasic GSIS.

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Section: Discussionmentioning

confidence: 99%

Syntaxin-3 regulates newcomer insulin granule exocytosis and compound fusion in pancreatic beta cells

et al. 2012

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“…2D). Compound vesicles have been observed in non-neuronal secretory cells (e.g., Alvarez de Toledo and Fernandez, 1990) and could potentially underlie the multivesicular release reported in bipolar cells (Singer et al, 2004) and cochlear hair cells (Glowatzki and Fuchs, 2002;Edmonds et al, 2004). On the other hand, it is difficult to reconcile the fusion of compound vesicles with the rise in membrane capacitance evoked by the rapid, global elevation of calcium, which is best described by a smooth, single exponential function indicative of the fusion of a small, homogeneous class of vesicle (Heidelberger et al, 1994).…”

Section: Fusion Scenarios and Ribbon Functionmentioning

confidence: 99%

Synaptic transmission at retinal ribbon synapses

Heidelberger

Thoreson

Witkovsky

2005

Progress in Retinal and Eye Research

206

231

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The molecular organization of ribbon synapses in photoreceptors and ON bipolar cells is reviewed in relation to the process of neurotransmitter release. The interactions between ribbon synapseassociated proteins, synaptic vesicle fusion machinery and the voltage-gated calcium channels that gate transmitter release at ribbon synapses are discussed in relation to the process of synaptic vesicle exocytosis. We describe structural and mechanistic specializations that permit the ON bipolar cell to release transmitter at a much higher rate than the photoreceptor does, under in vivo conditions. We also consider the modulation of exocytosis at photoreceptor synapses, with an emphasis on the regulation of calcium channels.

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“…For example, in the case of the massive exocytosis observed during mast cell degranulation (2), compound exocytosis would ensure that secretion occurs both through fusion of granules close to the plasma membrane and from deeper lying granules. This avoids the need to transport deeper granules up to the cell membrane and so would accelerate the secretory response.…”

mentioning

confidence: 99%

“…Granule-to-granule fusion can form large multigranular structures within the cell that then fuse with the plasma membrane. Capacitance measurements in mast cells show very large step increases that may be due to multigranular fusion (2). In contrast, in acinar cells (5) a mechanism termed sequential compound exocytosis occurs where the first (primary) granules fuse with the cell membrane, and this is followed by sequential fusion of other (secondary and tertiary) granules onto these primary granules (5,6).…”

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confidence: 99%

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Vesicle-associated Membrane Protein 8 (VAMP8) Is a SNARE (Soluble N-Ethylmaleimide-sensitive Factor Attachment Protein Receptor) Selectively Required for Sequential Granule-to-granule Fusion

Behrendorff

Dolai

Hong

et al. 2011

Journal of Biological Chemistry

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Compound exocytosis is found in many cell types and is the major form of regulated secretion in acinar and mast cells. Its key characteristic is the homotypic fusion of secretory granules. These then secrete their combined output through a single fusion pore to the outside. The control of compound exocytosis remains poorly understood. Although soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) such as syntaxin 2, SNAP23 (synaptosome-associated protein of 23 kDa), and SNAP25 have been suggested to play a role, none has been proven. Vesicle-associated membrane protein 8 (VAMP8) is a SNARE first associated with endocytic processes but more recently has been suggested as an R-SNARE in regulated exocytosis. Secretion in acinar cells is reduced when VAMP8 function is inhibited and is less in VAMP8 knock-out mice. Based on electron microscopy experiments, it was suggested that VAMP8 may be involved in compound exocytosis. Here we have tested the hypothesis that VAMP8 controls homotypic granule-to-granule fusion during sequential compound exocytosis. We use a new assay to distinguish primary fusion events (fusion with the cell membrane) from secondary fusion events (granule-granule fusion). Our data show the pancreatic acinar cells from VAMP8 knock-out animals have a specific reduction in secondary granule fusion but that primary granule fusion is unaffected. Furthermore, immunoprecipitation experiments show syntaxin 2 association with VAMP2, whereas syntaxin 3 associates with VAMP8. Taken together our data indicate that granule-to-granule fusion is regulated by VAMP8 containing SNARE complexes distinct from those that regulate primary granule fusion.The precise role of compound exocytosis has not been determined, but it is thought that it might enhance secretion by enabling fusion of, and release of contents from, granules that lie deeper within the cell (1). For example, in the case of the massive exocytosis observed during mast cell degranulation (2), compound exocytosis would ensure that secretion occurs both through fusion of granules close to the plasma membrane and from deeper lying granules. This avoids the need to transport deeper granules up to the cell membrane and so would accelerate the secretory response.In the case of acinar cells the apical plasma membrane area is relatively small compared with the total membrane area and is defined by tight junctional boundaries (3). Regulated exocytosis occurs exclusively at the apical membrane. Secretory (zymogen) granules are tightly packed in the apical region of acinar cells (see Fig. 1) and do not move over the minute timescales we use for stimulation. This means that only a few granules have direct access to the apical plasma membrane. Furthermore, granule fusion is so slow (many minutes) that close granules would limit access of deeper-lying granules to docking sites at the plasma membrane. Compound exocytosis provides a mechanism to enhance secretion by enabling deeper granules to fuse with peripheral granules and so release their c...

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Compound versus multigranular exocytosis in peritoneal mast cells.

Cited by 130 publications

References 17 publications

Syntaxin-3 regulates newcomer insulin granule exocytosis and compound fusion in pancreatic beta cells

Syntaxin-3 regulates newcomer insulin granule exocytosis and compound fusion in pancreatic beta cells

Synaptic transmission at retinal ribbon synapses

Vesicle-associated Membrane Protein 8 (VAMP8) Is a SNARE (Soluble N-Ethylmaleimide-sensitive Factor Attachment Protein Receptor) Selectively Required for Sequential Granule-to-granule Fusion

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