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Synergistic actions of v-SNARE transmembrane domains and membrane-curvature modifying lipids in neurotransmitter release

Vesicle fusion is mediated by assembly of SNARE proteins between opposing membranes. While previous work suggested an active role of SNARE transmembrane domains (TMDs) in promoting membrane merger (Dhara et al., 2016), the underlying mechanism remained elusive. Here, we show that naturally-occurring...

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Autores principales: Dhara, Madhurima, Mantero Martinez, Maria, Makke, Mazen, Schwarz, Yvonne, Mohrmann, Ralf, Bruns, Dieter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239655/
https://www.ncbi.nlm.nih.gov/pubmed/32391794
http://dx.doi.org/10.7554/eLife.55152
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author Dhara, Madhurima
Mantero Martinez, Maria
Makke, Mazen
Schwarz, Yvonne
Mohrmann, Ralf
Bruns, Dieter
author_facet Dhara, Madhurima
Mantero Martinez, Maria
Makke, Mazen
Schwarz, Yvonne
Mohrmann, Ralf
Bruns, Dieter
author_sort Dhara, Madhurima
collection PubMed
description Vesicle fusion is mediated by assembly of SNARE proteins between opposing membranes. While previous work suggested an active role of SNARE transmembrane domains (TMDs) in promoting membrane merger (Dhara et al., 2016), the underlying mechanism remained elusive. Here, we show that naturally-occurring v-SNARE TMD variants differentially regulate fusion pore dynamics in mouse chromaffin cells, indicating TMD flexibility as a mechanistic determinant that facilitates transmitter release from differentially-sized vesicles. Membrane curvature-promoting phospholipids like lysophosphatidylcholine or oleic acid profoundly alter pore expansion and fully rescue the decelerated fusion kinetics of TMD-rigidifying VAMP2 mutants. Thus, v-SNARE TMDs and phospholipids cooperate in supporting membrane curvature at the fusion pore neck. Oppositely, slowing of pore kinetics by the SNARE-regulator complexin-2 withstands the curvature-driven speeding of fusion, indicating that pore evolution is tightly coupled to progressive SNARE complex formation. Collectively, TMD-mediated support of membrane curvature and SNARE force-generated membrane bending promote fusion pore formation and expansion.
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spelling pubmed-72396552020-05-22 Synergistic actions of v-SNARE transmembrane domains and membrane-curvature modifying lipids in neurotransmitter release Dhara, Madhurima Mantero Martinez, Maria Makke, Mazen Schwarz, Yvonne Mohrmann, Ralf Bruns, Dieter eLife Neuroscience Vesicle fusion is mediated by assembly of SNARE proteins between opposing membranes. While previous work suggested an active role of SNARE transmembrane domains (TMDs) in promoting membrane merger (Dhara et al., 2016), the underlying mechanism remained elusive. Here, we show that naturally-occurring v-SNARE TMD variants differentially regulate fusion pore dynamics in mouse chromaffin cells, indicating TMD flexibility as a mechanistic determinant that facilitates transmitter release from differentially-sized vesicles. Membrane curvature-promoting phospholipids like lysophosphatidylcholine or oleic acid profoundly alter pore expansion and fully rescue the decelerated fusion kinetics of TMD-rigidifying VAMP2 mutants. Thus, v-SNARE TMDs and phospholipids cooperate in supporting membrane curvature at the fusion pore neck. Oppositely, slowing of pore kinetics by the SNARE-regulator complexin-2 withstands the curvature-driven speeding of fusion, indicating that pore evolution is tightly coupled to progressive SNARE complex formation. Collectively, TMD-mediated support of membrane curvature and SNARE force-generated membrane bending promote fusion pore formation and expansion. eLife Sciences Publications, Ltd 2020-05-11 /pmc/articles/PMC7239655/ /pubmed/32391794 http://dx.doi.org/10.7554/eLife.55152 Text en © 2020, Dhara et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Dhara, Madhurima
Mantero Martinez, Maria
Makke, Mazen
Schwarz, Yvonne
Mohrmann, Ralf
Bruns, Dieter
Synergistic actions of v-SNARE transmembrane domains and membrane-curvature modifying lipids in neurotransmitter release
title Synergistic actions of v-SNARE transmembrane domains and membrane-curvature modifying lipids in neurotransmitter release
title_full Synergistic actions of v-SNARE transmembrane domains and membrane-curvature modifying lipids in neurotransmitter release
title_fullStr Synergistic actions of v-SNARE transmembrane domains and membrane-curvature modifying lipids in neurotransmitter release
title_full_unstemmed Synergistic actions of v-SNARE transmembrane domains and membrane-curvature modifying lipids in neurotransmitter release
title_short Synergistic actions of v-SNARE transmembrane domains and membrane-curvature modifying lipids in neurotransmitter release
title_sort synergistic actions of v-snare transmembrane domains and membrane-curvature modifying lipids in neurotransmitter release
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239655/
https://www.ncbi.nlm.nih.gov/pubmed/32391794
http://dx.doi.org/10.7554/eLife.55152
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