SNAREs and traffic

Hong, Wanjin

doi:10.1016/j.bbamcr.2005.03.014

Cited by 539 publications

(661 citation statements)

References 167 publications

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“…Synaptobrevins (eg, Vamp1, Vamp2), syntaxins, and the synaptosomal‐associated protein Snap25 represent the main components of the SNARE (soluble N ‐ethylmaleimide‐sensitive factor attachment protein receptors) complex, which is involved in docking and fusion of synaptic vesicles with the presynaptic membrane at the central and the neuromuscular synapses 15, 16. Proteins belonging to this complex are involved in vesicle docking through the evolutionarily conserved active v‐SNARE coiled coil homology domain and present high sequence similarity across the different SNAREs 17, 18, 19…”

Section: Discussionmentioning

confidence: 99%

Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome

Salpietro

Lin

Vedove³

et al. 2017

Annals of Neurology

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We report 2 families with undiagnosed recessive presynaptic congenital myasthenic syndrome (CMS). Whole exome or genome sequencing identified segregating homozygous variants in VAMP1: c.51_64delAGGTGGGGGTCCCC in a Kuwaiti family and c.146G>C in an Israeli family. VAMP1 is crucial for vesicle fusion at presynaptic neuromuscular junction (NMJ). Electrodiagnostic examination showed severely low compound muscle action potentials and presynaptic impairment. We assessed the effect of the nonsense mutation on mRNA levels and evaluated the NMJ transmission in VAMP1 lew/lew mice, observing neurophysiological features of presynaptic impairment, similar to the patients. Taken together, our findings highlight VAMP1 homozygous mutations as a cause of presynaptic CMS. Ann Neurol 2017;81:597–603

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Section: Discussionmentioning

confidence: 99%

Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome

Salpietro

Lin

Vedove³

et al. 2017

Annals of Neurology

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“…Interestingly, expression of a dominant-interfering Exo70 protein or siRNA-mediated knockdowns did not prevent GLUT4 vesicle trafficking to the plasma membrane but did inhibit GLUT4 plasma membrane fusion whereas over expression of Sec6 and Sec8 enhanced GLUT4 translocation to the plasma membrane [33,35]. Although these data indicate that the Exocyst complex plays an important role in the insulin-regulated plasma membrane docking/tethering of GLUT4 vesicles, it is well established the physiologic minimal fusion machinery is dependent upon the assembly of the SNARE complex [36][37][38] SNARE proteins can be generally classified as v-SNAREs (or R-SNAREs) that possess a single coil-coiled domain and a transmembrane domain that are localized in vesicle compartment [39][40][41][42]. The second family, t-SNAREs (or Q-SNAREs) are dimeric, with one partner belongs to the family of syntaxin isoforms and the second partner belonging to the family of SNAP isoform.…”

Section: Glut4 Vesicle Docking and Plasma Membrane Fusionmentioning

confidence: 99%

Ins (endocytosis) and outs (exocytosis) of GLUT4 trafficking

Hou

Pessin

2007

Current Opinion in Cell Biology

132

116

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SummaryGlucose transporter 4 (GLUT4) is the major insulin regulated glucose transporter expressed mainly in muscle and adipose tissue. GLUT4 is stored in a poorly characterized intracellular vesicular compartment and translocates to the cell surface in response to insulin stimulation resulting in increase glucose uptake. This process is essential for the maintenance of normal glucose homeostasis and involves a complex interplay of trafficking events and intracellular signaling cascades. Recent studies have identified sortilin as an essential element for the formation of GLUT4 storage vesicles during adipogenesis and GGA (Golgi-localized γ-ear-containing Arf-binding protein) as a key coat adaptor for the entry of newly synthesized GLUT4 into the specialized compartment. Insulinstimulated GLUT4 translocation from this compartment to the plasma membrane appears to require the Akt/protein kinase B substrate, termed AS160 (Akt Substrate of 160 kDa). In addition, the VPS9 domain-containing protein Gapex-5 in complex with CIP4 appears to function as a Rab31 guanylnucleotide exchange factor that is necessary for insulin-stimulated GLUT4 translocation. Here we attempt to summaries recent advances in GLUT4 vesicle biogenesis, intracellular trafficking and membrane fusion.

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“…These SNARE proteins are produced in pancreatic beta cells and mediate similar putative steps in SG exocytosis [3]. Each vesicle (v)-and target (t)-membrane SNARE protein constitutes a large family of isoforms [4]. In beta cells, combinatorial matching of v-and t-SNARE isoforms may form the molecular basis of the distinct exocytotic events underlying the two phases of GSIS.…”

Section: Introductionmentioning

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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SNAREs and traffic

Cited by 539 publications

References 167 publications

Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome

Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome

Ins (endocytosis) and outs (exocytosis) of GLUT4 trafficking

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

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