Cleavage of members of the synaptobrevin/VAMP family by types D and F botulinal neurotoxins and tetanus toxin.

Yamasaki, Shinji; Baumeister, A.; Binz, Thomas; Blasi, Juan; Link, Egenhard; Cornille, Fabrice; Roques, B. P.; Fykse, Else Marie; Südhof, Thomas C.; Jahn, Reinhard

doi:10.1016/s0021-9258(18)99941-2

Cited by 243 publications

(43 citation statements)

References 38 publications

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“…Similar results were found using BoNT C that cleaves syntaxin, or BoNT A that cleaves SNAP-25 (Figure 1). In agreement with previously published data on release from synaptosomes, BoNT C and BoNT F were both more effective at inhibiting vesicle exocytosis than was BoNT A (McMahon et al, 1992;Yamasaki et al, 1994). Other NO donors, including S-nitrosocysteine (S-NC) and acidified sodium nitrite (SN), produced similar effects (data not shown).…”

Section: Effects Of Bonts On No-stimulated Vesicle Releasesupporting

confidence: 91%

“…BoNTs require a long incubation (90 min at tentiate VAMP binding to syntaxin 1a/GST without the 37ЊC) with synaptosomes, to be bound, internalized, and presence of SNAP-25, although this association has a for the enzymatically active light chain to gain access low affinity (Calakos et al, 1994;Pevsner et al, 1994b). to the cytosol (McMahon et al, 1992;Blasi et al, 1993a; It may be that NO is only capable of affecting binding Yamasaki et al, 1994). FM1-43 preloaded into synaptoin the conformation of this heterotrimer.…”

Section: No Potentiates Snap-25 and Vamp2 Binding To Syntaxin 1amentioning

confidence: 99%

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Nitric Oxide Modulates Synaptic Vesicle Docking/Fusion Reactions

Meffert

Calakos

Scheller

et al. 1996

Neuron

225

137

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Nitric oxide (NO) stimulates calcium-independent neurotransmitter release from synaptosomes. NO-stimulated release was found to be inhibited by Botulinum neurotoxins that inactivate the core complex of synaptic proteins involved in the docking and fusion of synaptic vesicles. In experiments using recombinant proteins, NO donors increased formation of the VAMP/SNAP-25/syntaxin 1a core complex and inhibited the binding of n-sec1 to syntaxin 1a. The combined effects of these activities is predicted to promote vesicle docking/fusion. The sulfhydryl reagent NEM inhibited the binding of n-sec1 to syntaxin 1a, while beta-ME could reverse the NO-enhanced association of VAMP/SNAP-25/syntaxin 1a. These data suggest that post-translational modification of sulfhydryl groups by a nitrogen monoxide (likely to be NO+) alters the synaptic protein interactions that regulate neurotransmitter release and synaptic plasticity.

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Section: Effects Of Bonts On No-stimulated Vesicle Releasesupporting

confidence: 91%

Section: No Potentiates Snap-25 and Vamp2 Binding To Syntaxin 1amentioning

confidence: 99%

Nitric Oxide Modulates Synaptic Vesicle Docking/Fusion Reactions

Meffert

Calakos

Scheller

et al. 1996

Neuron

225

137

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“…Due to the similarity between TeNTand BoNT/B, these results also suggest the possibility that the two copies of the SNARE motif of VAMP are paired in such a way that they adopt the same spatial orientation with respect to the Gln76^Phe77 bond (Pellizzari et al 1996). In addition, a basic region located after the cleavage site of TeNT and BoNT/B is important for their binding and optimal cleavage of VAMP (Shone et al 1993;Yamasaki et al 1994a;Cornille et al 1995Cornille et al , 1997; (v) the SNARE motif is also important for binding and proteolysis of SNAP-25 by BoNT/A and /E. The analysis of the rate of proteolysis of several SNAP-25 fragments deleted of SNARE motif(s) shows that the latter are hydrolysed, provided however that at least one the four copies of the motif is retained.…”

Section: Zinc-endopeptidase Activitymentioning

confidence: 74%

“…These antibodies crossreact among the three SNAREs and inhibit the proteolytic activity of the neurotoxins (Pellizzari et al 1996); (iii) the various neurotoxins cross-inhibit each other (Pellizzari et al 1996); (iv) proteolysis performed on sitedirected mutated VAMP or VAMP fragments indicates that the three carboxylate residues of the V2 copy of the motif are very important for the recognition by BoNT/B and /G, whereas those of the V1 copy are implicated in the recognition of BoNT/F and TeNT (Shone & Roberts 1994;Pellizzari et al 1996;Wictome et al 1996;Pellizzari et al 1997). BoNT/D shows a particular requirement for the Met46 present in V1 (Yamasaki et al 1994a;Pellizzari et al 1997). In view of the fact that V1 is more aminoterminal with respect to V2, these results explain why the minimal length of VAMP segments cleaved by TeNT is longer than that required by BoNT/B (Shone et al 1993;Foran et al 1994).…”

Section: Zinc-endopeptidase Activitymentioning

confidence: 99%

Tetanus and botulinum neurotoxins: mechanism of action and therapeutic uses

Pellizzari

Rossetto

Schiavo

et al. 1999

Phil. Trans. R. Soc. Lond. B

261

197

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The clostridial neurotoxins responsible for tetanus and botulism are proteins consisting of three domains endowed with di¡erent functions: neurospeci¢c binding, membrane translocation and proteolysis for speci¢c components of the neuroexocytosis apparatus. Tetanus neurotoxin (TeNT) binds to the presynaptic membrane of the neuromuscular junction, is internalized and transported retroaxonally to the spinal cord. The spastic paralysis induced by the toxin is due to the blockade of neurotransmitter release from spinal inhibitory interneurons. In contrast, the seven serotypes of botulinum neurotoxins (BoNTs) act at the periphery by inducing a £accid paralysis due to the inhibition of acetylcholine release at the neuromuscular junction. TeNT and BoNT serotypes B, D, F and G cleave speci¢cally at single but di¡erent peptide bonds, of the vesicle associated membrane protein (VAMP) synaptobrevin, a membrane protein of small synaptic vesicles (SSVs). BoNT types A, C and E cleave SNAP-25 at di¡erent sites located within the carboxyl-terminus, while BoNT type C additionally cleaves syntaxin. The remarkable speci¢city of BoNTs is exploited in the treatment of human diseases characterized by a hyperfunction of cholinergic terminals.

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“…We next examined the involvement of R-SNAREs in Cbln1 exocytosis by microRNA-based knockdown approaches. Since VAMP1, VAMP2, and VAMP3 are cleaved by TeNT (Yamasaki et al, 1994) and VAMP5 was not expressed in the cerebellum (Figure S3A), we focused on VAMP4, VAMP7, VAMP8, Sec22b, and Ykt6. Although VAMP7 represents TeNT-insensitive VAMPs, knocking down VAMP7 did not affect Cbln1 release even in the presence of TeNT to rule out compensatory pathways (Figure 4C).…”

Section: Activity-dependent Exocytosis Of Cbln1 Is Mediated By Distinct Snaresmentioning

confidence: 99%

Activity-Dependent Secretion of Synaptic Organizer Cbln1 from Lysosomes in Granule Cell Axons

Ibata

Kono

Narumi

et al. 2019

Neuron

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Synapse formation is achieved by various synaptic organizers. Although this process is highly regulated by neuronal activity, the underlying molecular mechanisms remain largely unclear. Here we show that Cbln1, a synaptic organizer of the C1q family, is released from lysosomes in axons but not dendrites of cerebellar granule cells in an activity-and Ca 2+dependent manner. Exocytosed Cbln1 was retained on axonal surfaces by binding to its presynaptic receptor neurexin. Cbln1 further diffused laterally along the axonal surface and accumulated at boutons by binding postsynaptic d2 glutamate receptors. Cbln1 exocytosis was insensitive to tetanus neurotoxin, accompanied by cathepsin B release, and decreased by disrupting lysosomes. Furthermore, overexpression of lysosomal sialidase Neu1 not only inhibited Cbln1 and cathepsin B exocytosis in vitro but also reduced axonal bouton formation in vivo. Our findings imply that co-release of Cbln1 and cathepsin B from lysosomes serves as a new mechanism of activity-dependent coordinated synapse modification.

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Cleavage of members of the synaptobrevin/VAMP family by types D and F botulinal neurotoxins and tetanus toxin.

Cited by 243 publications

References 38 publications

Nitric Oxide Modulates Synaptic Vesicle Docking/Fusion Reactions

Nitric Oxide Modulates Synaptic Vesicle Docking/Fusion Reactions

Tetanus and botulinum neurotoxins: mechanism of action and therapeutic uses

Activity-Dependent Secretion of Synaptic Organizer Cbln1 from Lysosomes in Granule Cell Axons

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