TY - JOUR
T1 - The synaptophysin/synaptobrevin complex dissociates independently of neuroexocytosis
AU - Reisinger, Clemens
AU - Yelamanchili, Sowmya V.
AU - Hinz, Britta
AU - Mitter, Diana
AU - Becher, Anja
AU - Bigalke, Hans
AU - Ahnert-Hilger, Gudrun
PY - 2004/7
Y1 - 2004/7
N2 - Synaptophysin is one of the most abundant membrane proteins of small synaptic vesicles. In mature nerve terminals it forms a complex with the vesicular membrane protein synaptobrevin, which appears to modulate synaptobrevin's interaction with the plasma membrane-associated proteins syntaxin and SNAP25 to form the SNARE complex as a prerequisite for membrane fusion. Here we show that synaptobrevin is preferentially cleaved by tetanus toxin while bound to synaptophysin or when existing as a homodimer. The synaptophysin/synaptobrevin complex is, however, not affected when neuronal secretion is blocked by botulinum A toxin which cleaves SNAP25. Excessive stimulation with α-latrotoxin or Ca2+-ionophores dissociates the synaptophysin/synaptobrevin complex and increases the interaction of the other SNARE proteins. The stimulation-induced dissociation of the synaptophysin/synaptobrevin complex is not inhibited by pre-incubating neurones with botulinum A toxin, but depends on extracellular calcium. However, the synaptophysin/synaptobrevin complex cannot be directly dissociated by calcium alone or in combination with magnesium. The dissociation of synaptobrevin from synaptophysin appears to precede its interaction with the other SNARE proteins and does not depend on the final fusion event. This finding further supports the modulatory role the synaptophysin/synaptobrevin complex may play in mature neurones.
AB - Synaptophysin is one of the most abundant membrane proteins of small synaptic vesicles. In mature nerve terminals it forms a complex with the vesicular membrane protein synaptobrevin, which appears to modulate synaptobrevin's interaction with the plasma membrane-associated proteins syntaxin and SNAP25 to form the SNARE complex as a prerequisite for membrane fusion. Here we show that synaptobrevin is preferentially cleaved by tetanus toxin while bound to synaptophysin or when existing as a homodimer. The synaptophysin/synaptobrevin complex is, however, not affected when neuronal secretion is blocked by botulinum A toxin which cleaves SNAP25. Excessive stimulation with α-latrotoxin or Ca2+-ionophores dissociates the synaptophysin/synaptobrevin complex and increases the interaction of the other SNARE proteins. The stimulation-induced dissociation of the synaptophysin/synaptobrevin complex is not inhibited by pre-incubating neurones with botulinum A toxin, but depends on extracellular calcium. However, the synaptophysin/synaptobrevin complex cannot be directly dissociated by calcium alone or in combination with magnesium. The dissociation of synaptobrevin from synaptophysin appears to precede its interaction with the other SNARE proteins and does not depend on the final fusion event. This finding further supports the modulatory role the synaptophysin/synaptobrevin complex may play in mature neurones.
KW - Clostridial neurotoxins
KW - Neuronal stimulation
KW - SNARE complex
KW - Synaptobrevin
KW - Synaptophysin
KW - Syp/Syb-complex
UR - http://www.scopus.com/inward/record.url?scp=3042807868&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3042807868&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2004.02472.x
DO - 10.1111/j.1471-4159.2004.02472.x
M3 - Article
C2 - 15198661
AN - SCOPUS:3042807868
SN - 0022-3042
VL - 90
SP - 1
EP - 8
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 1
ER -