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Analysis of SNARE-dependent Membrane Fusion

English title Analysis of SNARE-dependent Membrane Fusion
Applicant Mayer Andreas
Number 128661
Funding scheme Project funding (Div. I-III)
Research institution Centre Integratif de Genomique Faculté de Biologie et Médecine Université de Lausanne
Institution of higher education University of Lausanne - LA
Main discipline Biochemistry
Start/End 01.10.2009 - 30.09.2012
Approved amount 930'000.00
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All Disciplines (2)

Discipline
Biochemistry
Cellular Biology, Cytology

Keywords (7)

membrane fusion; vesicular traffic; organelle biogenesis; yeast; vacuole; exocytosis; secretion

Lay Summary (English)

Lead
Lay summary
Regulated membrane fusion controls physiology, because it is involved in secretion of hormones, neurotransmitters, growth factors, enzymes, receptors and transporters. These molecules are stored in intracellular vesicles that fuse with the plama membranes of cells in order to release these important cellular regulators. Also transport between intracellular compartments depends on cycles of vesicle formation and cargo loading on one organelle and the fusion of these vesicles, coupled to cargo delivery, at the target organelle.Membrane fusion in the endomembrane system depends on SNARE proteins. These SNAREs are essential for recognition and fusion between membranes. SNAREs interact with and are supported by a large number of additional proteins that control the binding and fusion of membranes. Yeast vacuoles revealed that fusion can depend on the membrane-integral V0 sector of the V-type H+-ATPase. This surprising finding was confirmed in higher eukaryotes: For the secretion of neurotransmitters, insulin, and multivesicular body content, and for phagosome-lysosome fusion. Vacuole fusion has the advantage of allowing assay of several intermediates and of fusion protein interactions at different steps of the fusion reaction. We will combine the excellent molecular dissection of the vacuolar fusion machinery with genetic approaches in order to investigate how V0, SNAREs and their interactions influence the substeps of a membrane fusion reaction, lipid transition (hemifusion), its subsequent progression to a fusion pore and the stability and final enlargement of this pore. Furthermore we will test how another class of conserved SNARE-interacting proteins, the SM proteins, affects the SNAREs at these different steps.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Identification of Genes Affecting Vacuole Membrane Fragmentation in Saccharomyces cerevisiae.
Michaillat Lydie, Mayer Andreas (2013), Identification of Genes Affecting Vacuole Membrane Fragmentation in Saccharomyces cerevisiae., in PloS one, 8(2), 54160-54160.
Identification of Genes Affecting Vacuole Membrane Fragmentation in Saccharomyces cerevisiae.
Michaillat Lydie, Mayer Andreas (2013), Identification of Genes Affecting Vacuole Membrane Fragmentation in Saccharomyces cerevisiae., in PloS one, 8(2), 54160-54160.
Yeast vacuoles fragment in an asymmetrical two-phase process with distinct protein requirements.
Zieger Martin, Mayer Andreas (2012), Yeast vacuoles fragment in an asymmetrical two-phase process with distinct protein requirements., in Molecular biology of the cell, 23(17), 3438-49.
Cell-free reconstitution of vacuole membrane fragmentation reveals regulation of vacuole size and number by TORC1.
Michaillat Lydie, Baars Tonie Luise, Mayer Andreas (2012), Cell-free reconstitution of vacuole membrane fragmentation reveals regulation of vacuole size and number by TORC1., in Molecular biology of the cell, 23(5), 881-95.
Sequential analysis of trans-SNARE formation in intracellular membrane fusion.
Alpadi Kannan, Kulkarni Aditya, Comte Veronique, Reinhardt Monique, Schmidt Andrea, Namjoshi Sarita, Mayer Andreas, Peters Christopher (2012), Sequential analysis of trans-SNARE formation in intracellular membrane fusion., in PLoS biology, 10(1), 1001243-1001243.
The V-ATPase proteolipid cylinder promotes the lipid-mixing stage of SNARE-dependent fusion of yeast vacuoles.
Strasser Bernd, Iwaszkiewicz Justyna, Michielin Olivier, Mayer Andreas (2011), The V-ATPase proteolipid cylinder promotes the lipid-mixing stage of SNARE-dependent fusion of yeast vacuoles., in The EMBO journal, 30(20), 4126-41.
Microautophagy of the nucleus coincides with a vacuolar diffusion barrier at nuclear-vacuolar junctions.
Dawaliby Rosie, Mayer Andreas (2010), Microautophagy of the nucleus coincides with a vacuolar diffusion barrier at nuclear-vacuolar junctions., in Molecular biology of the cell, 21(23), 4173-83.
The SM protein Vps33 and the t-SNARE H(abc) domain promote fusion pore opening.
Pieren Michel, Schmidt Andrea, Mayer Andreas (2010), The SM protein Vps33 and the t-SNARE H(abc) domain promote fusion pore opening., in Nature structural & molecular biology, 17(6), 710-7.
Dynamin-SNARE interactions control trans-SNARE formation in intracellular membrane fusion
Alpadi K., Kulkarni A., Namjoshi S., Srinivasan S., Sippel K., Ayscough K., Zieger M., Schmidt A., Mayer A., Quiocho F., Peters C., Dynamin-SNARE interactions control trans-SNARE formation in intracellular membrane fusion, in Nature Communications.

Collaboration

Group / person Country
Types of collaboration
Max-Planck-Gesellschaft Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
ETHZ Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
University Osnabrück Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
MRC Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
UNIGE Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
UNIFR Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Eurofed Lipid Conference 16.05.2012 Bern
Gordon Research Conference Bioenergetics 26.06.2011 Proctor Academy, USA
Annual Meeting Exo-/Endocytose 25.05.2011 Padua, Italy
Genetics Society, 26th Fungal Genetics Conference 15.03.2011 Asilomar, USA
Annual Meeting of the ASCB 11.12.2010 Philadelphia, USA
Yeast Genetics and Molecular Biology Meeting 27.07.2010 Vancouver, Canada
Gordon Research Conference on Lysosomes & Endocytosis 20.06.2010 Andover, USA
Annual Meeting Exo-/Endocytose 03.06.2010 Gerardmer, Frankreich
COST Action CM0801 Meeting 28.05.2010 Siena, Italy
8th EMBO-Annaberg Conference on Protein and Lipid Function in secretion and endocytosis 12.01.2010 Goldegg, Austria
5th International Symposium on Autophagy 23.10.2009 Kyoto


Awards

Title Year
Jürg-Tschopp-Award 2012

Patents

Title Date Number Inventor Owner
Materials and methods for treating and/or preventing a disease caused by a polyphosphate producing e 20.12.2011 US patent appl. 61/436,721

Associated projects

Number Title Start Funding scheme
144258 Cooperation of V-ATPase V0 sector with SNAREs in membrane fusion 01.10.2012 Project funding (Div. I-III)
145002 Microscale thermophoresis for the Faculty of Bology and Medicine in Lausanne 01.12.2012 R'EQUIP
113752 Analysis of SNARE-dependent Membrane Fusion 01.10.2006 Project funding (Div. I-III)
144258 Cooperation of V-ATPase V0 sector with SNAREs in membrane fusion 01.10.2012 Project funding (Div. I-III)

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