Munc18-bound syntaxin readily forms SNARE complexes with synaptobrevin in native plasma membranes
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Munc18-bound syntaxin readily forms SNARE complexes with synaptobrevin in native plasma membranes. / Zilly, Felipe E; Sørensen, Jakob B; Jahn, Reinhard; Lang, Thorsten.
In: PLoS - Biology, Vol. 4, No. 10, 2006, p. e330.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Munc18-bound syntaxin readily forms SNARE complexes with synaptobrevin in native plasma membranes
AU - Zilly, Felipe E
AU - Sørensen, Jakob B
AU - Jahn, Reinhard
AU - Lang, Thorsten
N1 - Keywords: Animals; Binding Sites; Cell Membrane; Microscopy, Fluorescence; Models, Biological; Munc18 Proteins; PC12 Cells; Plasmids; Protein Binding; Qa-SNARE Proteins; R-SNARE Proteins; Rats; Recombinant Proteins; SNARE Proteins; Vesicle-Associated Membrane Protein 2
PY - 2006
Y1 - 2006
N2 - Munc18-1, a protein essential for regulated exocytosis in neurons and neuroendocrine cells, belongs to the family of Sec1/Munc18-like (SM) proteins. In vitro, Munc18-1 forms a tight complex with the SNARE syntaxin 1, in which syntaxin is stabilized in a closed conformation. Since closed syntaxin is unable to interact with its partner SNAREs SNAP-25 and synaptobrevin as required for membrane fusion, it has hitherto not been possible to reconcile binding of Munc18-1 to syntaxin 1 with its biological function. We now show that in intact and exocytosis-competent lawns of plasma membrane, Munc18-1 forms a complex with syntaxin that allows formation of SNARE complexes. Munc18-1 associated with membrane-bound syntaxin 1 can be effectively displaced by adding recombinant synaptobrevin but not syntaxin 1 or SNAP-25. Displacement requires the presence of endogenous SNAP-25 since no displacement is observed when chromaffin cell membranes from SNAP-25-deficient mice are used. We conclude that Munc18-1 allows for the formation of a complex between syntaxin and SNAP-25 that serves as an acceptor for vesicle-bound synaptobrevin and that thus represents an intermediate in the pathway towards exocytosis.
AB - Munc18-1, a protein essential for regulated exocytosis in neurons and neuroendocrine cells, belongs to the family of Sec1/Munc18-like (SM) proteins. In vitro, Munc18-1 forms a tight complex with the SNARE syntaxin 1, in which syntaxin is stabilized in a closed conformation. Since closed syntaxin is unable to interact with its partner SNAREs SNAP-25 and synaptobrevin as required for membrane fusion, it has hitherto not been possible to reconcile binding of Munc18-1 to syntaxin 1 with its biological function. We now show that in intact and exocytosis-competent lawns of plasma membrane, Munc18-1 forms a complex with syntaxin that allows formation of SNARE complexes. Munc18-1 associated with membrane-bound syntaxin 1 can be effectively displaced by adding recombinant synaptobrevin but not syntaxin 1 or SNAP-25. Displacement requires the presence of endogenous SNAP-25 since no displacement is observed when chromaffin cell membranes from SNAP-25-deficient mice are used. We conclude that Munc18-1 allows for the formation of a complex between syntaxin and SNAP-25 that serves as an acceptor for vesicle-bound synaptobrevin and that thus represents an intermediate in the pathway towards exocytosis.
U2 - 10.1371/journal.pbio.0040330
DO - 10.1371/journal.pbio.0040330
M3 - Journal article
C2 - 17002520
VL - 4
SP - e330
JO - PLoS Biology
JF - PLoS Biology
SN - 1544-9173
IS - 10
ER -
ID: 16835426