The molecular machinery for fast and slow neurosecretion

Martin, Thomas F.J.

doi:10.1016/0959-4388(94)90002-7

Cited by 80 publications

(42 citation statements)

References 73 publications

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“…There are other soluble proteins that are involved in exocytosis, but, owing to space constraints, this Review will focus on SNARE proteins. 33,34 In nerve terminals affected by BTX, the light chain cleaves specific peptide bonds in the synaptic fusion complex, preventing exocytosis of the acetylcholine vesicle at the nerve terminal, and therefore inhibiting neurotransmission and muscle contraction ( Figure 3D-F). 32 Each BTX serotype cleaves a distinct protein site; BTX-A cleaves SNAP-25.…”

Section: Exocytosis Inhibitionmentioning

confidence: 99%

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

et al. 2008

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SUMMARYBotulinum toxins can effectively and selectively disrupt and modulate neurotransmission in striated muscle. Recently, urologists have become interested in the use of these toxins in patients with detrusor overactivity and other urological disorders. In both striated and smooth muscle, botulinum toxin A (BTX-A) is internalized by presynaptic neurons after binding to an extracellular receptor (ganglioside and presumably synaptic vesicle protein 2C). In the neuronal cytosol, BTX-A disrupts fusion of the acetylcholine-containing vesicle with the neuronal wall by cleaving the SNAP-25 protein in the synaptic fusion complex. The net effect is selective paralysis of the low-grade contractions of the unstable detrusor, while still allowing high-grade contraction that initiates micturition. Additionally, BTX-A seems to have effects on afferent nerve activity by modulating the release of ATP in the urothelium, blocking the release of substance P, calcitonin gene-related peptide and glutamate from afferent nerves, and reducing levels of nerve growth factor. These effects on sensory feedback loops might not only help to explain the mechanism of BTX-A in relieving symptoms of overactive bladder, but also suggest a potential role for BTX-A in the relief of hyperalgesia associated with lower urinary tract disorders.

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Section: Exocytosis Inhibitionmentioning

confidence: 99%

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

et al. 2008

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“…Neurotransmitter release is triggered by calcium influx through voltage-gated calcium channels, and much progress has been achieved in recent years in identifying proteins and proteinprotein interactions involved in the trafficking, docking, and calcium-dependent exocytosis of secretory vesicles (for review, see Martin, 1994;Sudhof, 1995;Augustine et al, 1996).…”

Section: Abstract: Cysteine String Proteins; Vamp; Calcium Channels;mentioning

confidence: 99%

Cysteine String Proteins Associated with Secretory Granules of the Rat Neurohypophysis

et al. 1997

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The properties and subcellular distribution of cysteine string proteins (csps) were analyzed in peptidergic nerve terminals of the rat neurohypophysis. Polyclonal antibodies raised against recombinant rat brain csp recognized a 36 kDa protein in isolated neurosecretosomes from the post-pituitary. After chemical deacylation, a single 27 kDa form was detected that displayed identical properties to csps in a whole-brain synaptosomal fraction. Immunoisolation demonstrated that synaptophysin and csps were located in the same vesicles. Density gradient centrifugation of postsynaptosomal supernatants of neurohypophysial homogenates revealed that csps and VAMP were present in two distinct vesicle populations. Synaptophysin was only detected in the slowly migrating population corresponding to small synaptic vesicles, whereas arginine vasopressin was present in the more rapidly sedimenting population indicating that it contains large dense core vesicles (LDCVs). Immobilized antibodies against csp, synaptotagmin, or VAMP captured vesicular arginine vasopressin confirming the association of these proteins with LDCVs. Co-immunoprecipitation assays with proteins solubilized from neurohypophysial or whole-brain nerve terminals failed to reveal complexes containing csp and [ 125 I]GVIA receptors. These results indicate that csps in the CNS are associated with both small synaptic vesicles and LDCVs. However, they do not provide support for the hypothesis that protein complexes implicated in exocytosis, which interact with presynaptic N-type calcium channels, contain csps.

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“…Analogies have been made to the mechanism of regulated synaptic vesicle exocytosis in neurons to help identify proteins that are necessary for the control of insulin exocytosis, and indeed there are similar protein isoforms involved (Burgoyne & Morgan 2003). However, there are significant differences in the mechanisms of synaptic-like vesicle exocytosis versus that of large dense-core secretory vesicles (LDCV), such as the insulin-containing -granules found in -cells (Martin 1994, Edwardson & Marciniak 1995. While common proteins catalyze both processes (e.g.…”

Section: Introductionmentioning

confidence: 99%

Intragranular targeting of syncollin, but not a syncollinGFP chimera, inhibits regulated insulin exocytosis in pancreatic β-cells

Hays¹,

Wicksteed²,

Y³

et al. 2005

Journal of Endocrinology

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Several proteins play a role in the mechanism of insulin exocytosis. However, these 'exocytotic proteins' have yet to account for the regulated aspect of insulin exocytosis, and other factors are involved. In pancreatic exocrine cells, the intralumenal zymogen granule protein, syncollin, is required for efficient regulated exocytosis, but it is not known whether intragranular peptides similarly influence regulated insulin exocytosis. Here, this issue has been addressed using expression of syncollin and a syncollingreen fluorescent protein (syncollinGFP) chimera in rat islet -cells as experimental tools. Syncollin is not normally expressed in -cells but adenoviral-mediated expression of both syncollin and syncollinGFP indicated that these were specifically targeted to the lumen of -granules. Syncollin expression in isolated rat islets had no effect on basal insulin secretion but significantly inhibited regulated insulin secretion stimulated by glucose (16·7 mM), glucagon-like peptide-1 (GLP-1) (10 nM) and glyburide (5µM). Consistent with specific localization of syncollin to -granules, constitutive secretion was unchanged by syncollin expression in rat islets. Syncollin-mediated inhibition of insulin secretion was not due to inadequate insulin production. Moreover, secretagogue-induced increases in cytosolic intracellular Ca 2+, which is a prerequisite for triggering insulin exocytosis, were unaffected in syncollin-expressing islets. Therefore, syncollin was most likely acting downstream of secondary signals at the level of insulin exocytosis. Thus, syncollin expression in -cells has highlighted the importance of intralumenal -granule peptide factors playing a role in the control of insulin exocytosis. In contrast to syncollin, syncollinGFP had no effect on insulin secretion, underlining its usefulness as a 'fluorescent tag' to track -granule transport and exocytosis in real time.

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The molecular machinery for fast and slow neurosecretion

Cited by 80 publications

References 73 publications

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

Drug Insight: biological effects of botulinum toxin A in the lower urinary tract

Cysteine String Proteins Associated with Secretory Granules of the Rat Neurohypophysis

Intragranular targeting of syncollin, but not a syncollinGFP chimera, inhibits regulated insulin exocytosis in pancreatic β-cells

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