Munc18-bound syntaxin readily forms SNARE complexes with synaptobrevin in native plasma membranes.
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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2006-10-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.0040330 |
| _version_ | 1818742302500192256 |
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| author | Felipe E Zilly Jakob B Sørensen Reinhard Jahn Thorsten Lang |
| author_facet | Felipe E Zilly Jakob B Sørensen Reinhard Jahn Thorsten Lang |
| author_sort | Felipe E Zilly |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-18T02:10:22Z |
| format | Article |
| id | doaj.art-74b09e247649439991236c491b6ea3f9 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-18T02:10:22Z |
| publishDate | 2006-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-74b09e247649439991236c491b6ea3f92022-12-21T21:24:30ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852006-10-01410e33010.1371/journal.pbio.0040330Munc18-bound syntaxin readily forms SNARE complexes with synaptobrevin in native plasma membranes.Felipe E ZillyJakob B SørensenReinhard JahnThorsten LangMunc18-1, 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.https://doi.org/10.1371/journal.pbio.0040330 |
| spellingShingle | Felipe E Zilly Jakob B Sørensen Reinhard Jahn Thorsten Lang Munc18-bound syntaxin readily forms SNARE complexes with synaptobrevin in native plasma membranes. PLoS Biology |
| title | Munc18-bound syntaxin readily forms SNARE complexes with synaptobrevin in native plasma membranes. |
| title_full | Munc18-bound syntaxin readily forms SNARE complexes with synaptobrevin in native plasma membranes. |
| title_fullStr | Munc18-bound syntaxin readily forms SNARE complexes with synaptobrevin in native plasma membranes. |
| title_full_unstemmed | Munc18-bound syntaxin readily forms SNARE complexes with synaptobrevin in native plasma membranes. |
| title_short | Munc18-bound syntaxin readily forms SNARE complexes with synaptobrevin in native plasma membranes. |
| title_sort | munc18 bound syntaxin readily forms snare complexes with synaptobrevin in native plasma membranes |
| url | https://doi.org/10.1371/journal.pbio.0040330 |
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