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

Tetanus toxin (TeTx) and the various forms of botulinal neurotoxins (BoNT/A to BoNT/G) potently inhibit neurotransmission by means of their L chains which selectively proteolyze synaptic proteins such as synaptobrevin (TeTx, BoNT/B, BoNT/F), SNAP-25 (BoNT/A), and syntaxin (BoNT/C1). Here we show tha...

Descripción completa

Detalles Bibliográficos
Autores: Yamasaki, Shiqji, Binz, Thomas, Baumeister, Anja, Blasi Cabús, Joan, Link, Egenhard, Cornille, Fabrice, Roques, Bernard, Südhof, Thomas C., Jahn, Reinhard, Niemann, Heiner, Fykse, Else Marie
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:1994
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/177129
Acceso en línea:https://hdl.handle.net/2445/177129
Access Level:acceso abierto
Palabra clave:Toxina botulínica
Farmacologia
Proteïnes de membrana
Teixit nerviós
Toxina tetànica
Botulinum toxin
Pharmacology
Membrane proteins
Nerve tissue
Tetanus toxin
id ES_3ec25be80485aba76514eb599fc4e05b
oai_identifier_str oai:diposit.ub.edu:2445/177129
network_acronym_str ES
network_name_str España
repository_id_str
spelling Cleavage of members of the synaptobrevin family by botulinum neurotoxin type D Cleavage of members of the synaptobrevin/VAMP family by types D and F botulinal neurotoxins and tetanus toxinYamasaki, ShiqjiBinz, ThomasBaumeister, AnjaBlasi Cabús, JoanLink, EgenhardCornille, FabriceRoques, BernardSüdhof, Thomas C.Jahn, ReinhardNiemann, HeinerFykse, Else MarieToxina botulínicaFarmacologiaProteïnes de membranaTeixit nerviósToxina tetànicaBotulinum toxinPharmacologyMembrane proteinsNerve tissueTetanus toxinTetanus toxin (TeTx) and the various forms of botulinal neurotoxins (BoNT/A to BoNT/G) potently inhibit neurotransmission by means of their L chains which selectively proteolyze synaptic proteins such as synaptobrevin (TeTx, BoNT/B, BoNT/F), SNAP-25 (BoNT/A), and syntaxin (BoNT/C1). Here we show that BoNT/D cleaves rat synaptobrevin 1 and 2 in toxified synaptosomes and in isolated vesicles. In contrast, synaptobrevin 1, as generated by in vitro translation, is only a poor substrate for BoNT/D, whereas this species is cleaved by BoNT/F with similar potency. Cleavage by BoNT/D occurs at the peptide bond Lys59-Leu60 which is adjacent to the BoNT/F cleavage site (Gln58-Lys59) and again differs from the site hydrolyzed by TeTx and BoNT/B (Gln76-Phe77). Cellubrevin, a recently discovered isoform expressed outside the nervous system, is efficiently cleaved by all three toxins examined. For further characterization of the substrate requirements of BoNT/D, we tested amino- and carboxyl-terminal deletion mutants of synaptobrevin 2 as well as synthetic peptides. Shorter peptides containing up to 15 amino acids on either side of the cleavage site were not cleaved, and a peptide extending from Arg47 to Thr116 was a poor substrate for all three toxins tested. However, cleavability was restored when the peptide is further extended at the NH2 terminus (Thr27-Thr116) demonstrating that NH2 terminally located sequences of synaptobrevin which are distal from the respective cleavage sites are required for proteolysis. To further examine the isoform specificity, several mutants of rat synaptobrevin 2 were generated in which individual amino acids were replaced with those found in rat synaptobrevin 1. We show that a Met46 to Ile46 substitution drastically diminishes cleavability by BoNT/D and that the presence of Val76 instead of Gln76 dictates the reduced cleavability of synaptobrevin isoforms by TeTx.American Society for Biochemistry and Molecular Biology1994info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/177129Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/S0021-9258(18)99941-2Journal of Biological Chemistry, 1994, vol. 269, num. 17, p. 12764-12772https://doi.org/10.1016/S0021-9258(18)99941-2(c) American Society for Biochemistry and Molecular Biology, 1994info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1771292026-05-27T06:46:51Z
dc.title.none.fl_str_mv Cleavage of members of the synaptobrevin family by botulinum neurotoxin type D Cleavage of members of the synaptobrevin/VAMP family by types D and F botulinal neurotoxins and tetanus toxin
title Cleavage of members of the synaptobrevin family by botulinum neurotoxin type D Cleavage of members of the synaptobrevin/VAMP family by types D and F botulinal neurotoxins and tetanus toxin
spellingShingle Cleavage of members of the synaptobrevin family by botulinum neurotoxin type D Cleavage of members of the synaptobrevin/VAMP family by types D and F botulinal neurotoxins and tetanus toxin
Yamasaki, Shiqji
Toxina botulínica
Farmacologia
Proteïnes de membrana
Teixit nerviós
Toxina tetànica
Botulinum toxin
Pharmacology
Membrane proteins
Nerve tissue
Tetanus toxin
title_short Cleavage of members of the synaptobrevin family by botulinum neurotoxin type D Cleavage of members of the synaptobrevin/VAMP family by types D and F botulinal neurotoxins and tetanus toxin
title_full Cleavage of members of the synaptobrevin family by botulinum neurotoxin type D Cleavage of members of the synaptobrevin/VAMP family by types D and F botulinal neurotoxins and tetanus toxin
title_fullStr Cleavage of members of the synaptobrevin family by botulinum neurotoxin type D Cleavage of members of the synaptobrevin/VAMP family by types D and F botulinal neurotoxins and tetanus toxin
title_full_unstemmed Cleavage of members of the synaptobrevin family by botulinum neurotoxin type D Cleavage of members of the synaptobrevin/VAMP family by types D and F botulinal neurotoxins and tetanus toxin
title_sort Cleavage of members of the synaptobrevin family by botulinum neurotoxin type D Cleavage of members of the synaptobrevin/VAMP family by types D and F botulinal neurotoxins and tetanus toxin
dc.creator.none.fl_str_mv Yamasaki, Shiqji
Binz, Thomas
Baumeister, Anja
Blasi Cabús, Joan
Link, Egenhard
Cornille, Fabrice
Roques, Bernard
Südhof, Thomas C.
Jahn, Reinhard
Niemann, Heiner
Fykse, Else Marie
author Yamasaki, Shiqji
author_facet Yamasaki, Shiqji
Binz, Thomas
Baumeister, Anja
Blasi Cabús, Joan
Link, Egenhard
Cornille, Fabrice
Roques, Bernard
Südhof, Thomas C.
Jahn, Reinhard
Niemann, Heiner
Fykse, Else Marie
author_role author
author2 Binz, Thomas
Baumeister, Anja
Blasi Cabús, Joan
Link, Egenhard
Cornille, Fabrice
Roques, Bernard
Südhof, Thomas C.
Jahn, Reinhard
Niemann, Heiner
Fykse, Else Marie
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Toxina botulínica
Farmacologia
Proteïnes de membrana
Teixit nerviós
Toxina tetànica
Botulinum toxin
Pharmacology
Membrane proteins
Nerve tissue
Tetanus toxin
topic Toxina botulínica
Farmacologia
Proteïnes de membrana
Teixit nerviós
Toxina tetànica
Botulinum toxin
Pharmacology
Membrane proteins
Nerve tissue
Tetanus toxin
description Tetanus toxin (TeTx) and the various forms of botulinal neurotoxins (BoNT/A to BoNT/G) potently inhibit neurotransmission by means of their L chains which selectively proteolyze synaptic proteins such as synaptobrevin (TeTx, BoNT/B, BoNT/F), SNAP-25 (BoNT/A), and syntaxin (BoNT/C1). Here we show that BoNT/D cleaves rat synaptobrevin 1 and 2 in toxified synaptosomes and in isolated vesicles. In contrast, synaptobrevin 1, as generated by in vitro translation, is only a poor substrate for BoNT/D, whereas this species is cleaved by BoNT/F with similar potency. Cleavage by BoNT/D occurs at the peptide bond Lys59-Leu60 which is adjacent to the BoNT/F cleavage site (Gln58-Lys59) and again differs from the site hydrolyzed by TeTx and BoNT/B (Gln76-Phe77). Cellubrevin, a recently discovered isoform expressed outside the nervous system, is efficiently cleaved by all three toxins examined. For further characterization of the substrate requirements of BoNT/D, we tested amino- and carboxyl-terminal deletion mutants of synaptobrevin 2 as well as synthetic peptides. Shorter peptides containing up to 15 amino acids on either side of the cleavage site were not cleaved, and a peptide extending from Arg47 to Thr116 was a poor substrate for all three toxins tested. However, cleavability was restored when the peptide is further extended at the NH2 terminus (Thr27-Thr116) demonstrating that NH2 terminally located sequences of synaptobrevin which are distal from the respective cleavage sites are required for proteolysis. To further examine the isoform specificity, several mutants of rat synaptobrevin 2 were generated in which individual amino acids were replaced with those found in rat synaptobrevin 1. We show that a Met46 to Ile46 substitution drastically diminishes cleavability by BoNT/D and that the presence of Val76 instead of Gln76 dictates the reduced cleavability of synaptobrevin isoforms by TeTx.
publishDate 1994
dc.date.none.fl_str_mv 1994
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/177129
url https://hdl.handle.net/2445/177129
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/S0021-9258(18)99941-2
Journal of Biological Chemistry, 1994, vol. 269, num. 17, p. 12764-12772
https://doi.org/10.1016/S0021-9258(18)99941-2
dc.rights.none.fl_str_mv (c) American Society for Biochemistry and Molecular Biology, 1994
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Society for Biochemistry and Molecular Biology, 1994
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869406574509817856
score 15.301629

Similares en LA Referencia