 Associate Professor Fred Meunier Contact: f.meunier@uq.edu.au Lab Media Release 20 Oct 2008 -- Scientific hunch poised to save thousands from toxic fish poisoning Post-Doctoral Scientists Tam Nguyen VISITING SCIENTISTS Dr Alain Chan DOCTORAL STUDENTS Peter Wen “Dynamic role of PI3P in neurosecretion” Shari Daniels (Doctorate of Clinical Dentistry (Orthodontics) Research) Mitja Schenning “Dynamic roles of N-type Ca2+ channel during neurotransmitter release” Nancy Honesta T Malintan “Functional Role of Munc18a in neuronal secretion” Michelle Christie (shared student) “mapping interactions between purified proteins involved in membrane fusion” Honours Students Rachel Gormal
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Associate Professor Fred Meunier
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PI3 kinase-C2α We have discovered that in neurosecretory cells, PI3 kinase-C2α, which produces the lipid PtdIns3P, was enriched on secretory vesicles and that its activity was critical for ATP-dependent priming of secretory vesicles - a process by which vesicles acquire the ability to fuse with the plasma membrane (Meunier et al., MBC, 2005). |
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Phosphoinositide pull down We have recently developed a novel phosphoinositide pull down strategy coupled with mass spectrometry that allows us to identify selective PI binding proteins from highly purified subcellular fractions. This method has the potential to reveal important cellular PI effectors in a variety of organelle and cellular systems. We have already identified PtdIns(4,5)P2 effectors for exocytosis in purified chromaffin granules (Osborne et al., MCP). |
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Mechanism of neuroexocytosis and synaptic plasticity [top] |
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t-SNARE clusters We have recently demonstrated that Syntaxin1A and SNAP25 interacts to form t-SNARE heterodimers organized in clusters on the plasma membrane of neurosecretory cells (Rickman et al., JBC, 2004). We are in the process of investigating the molecular pathway controlling the number and size of these t-SNARE clusters. |
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Munc18 One aspect of that work deals with the mysterious role played by Munc18a in controling exocytosis. We recently demonstrated that the polyunsaturated fatty acid arachidonic acid was capable of promoting Munc18a binding to the SNARE complex, thereby mimicking the binding pattern of all other members of the Munc18 family (Latham et al., JNC, 2006). |
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Glycerotoxin To sustain a high level of neuronal activity exocytosis of synaptic vesicles is closely followed by endocytosis. To investigate the molecular mechanism coupling the two processes, we have purified a novel neurotoxin called Glycerotoxin (Meunier et al., EMBO J, 2002) capable of greatly increasing both exocytosis and endocytosis (Schenning et al., J Neurochem, 2006). We are currently using this tool to investigate the mechanism of synaptic vesicle recycling under sustained stimulation of neurotransmitter release. |
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Biotechnology to help treat motoneuronal diseases Motoneuronal diseases are notoriously difficult to treat and one of the main hindrances to treatment is the relative inaccessibility of motoneurons. We are designing probes to deliver fluorescently-labelled molecules specifically in motoneurons. |
Recent Selected Publications [top]
Osborne S.L., Wen P.J., Boucheron C., Nguyen H.N., Hayakawa M., Kaizawa H., Parker P.J., Vitale N., and Meunier F.A. (2008). PIKfyve negatively regulates exocytosis in neurosecretory cells. J. Biol. Chem Epub ahead of print.
Osborne S.L., Wallis T.P., Jimenez J.L., Gorman J.J. and Meunier F.A. (2007). Identification of secretory granule phosphatidylinositol 4,5-bisphosphate-interacting proteins using an affinity pulldown strategy. Mol. Cell Proteomics 6:1158-1169.
Latham C.F., Osborne S.L., Cryle M.J., and Meunier F.A. (2006). Arachidonic acid potentiates exocytosis and allows neuronal SNARE complex to interact with Munc18a. J Neurochem. 100:1543-54.
Schenning M, Proctor DT, Ragnarsson L, Barbier J, Lavidis NA, Molgo J, Zamponi GW, Schiavo G, and Meunier, F.A. (2006). Glycerotoxin stimulates neurotransmitter release from N-type Ca2+ channel expressing neurons. J Neurochem. 98:894-904.
Rickman C., Meunier F.A., Binz T. and Davletov B.A. (2004). High affinity interaction of syntaxin and SNAP-25 on the plasma membrane is abolished by botulinum toxin E. J. Biol. Chem. 279: 644-651.
Meunier F.A., Osborne S.L., Hammond G., Cooke F.T., Parker P.J., Domin J. and Schiavo G. (2005). PI3-kinase C2 is essential for ATP-dependent priming of neurosecretory granule exocytosis. Mol Biol Cell. 16:4841-51.
Meunier F.A., Lisk G., Sesardic D. and Dolly J.O. (2003). Dynamics of motor nerve terminal remodeling unveiled using SNARE-cleaving botulinum toxins. Molecular Cellular Neuroscience 22: 454-466.
Meunier F.A., Feng Z.P., Molgo J., Zamponi G. and Schiavo G. (2002). Glycerotoxin from Glycera convoluta stimulates neurosecretion by targeting N-type Ca2+ channels Cav2.2. EMBO J. 21: 6733-6743.
Meunier F.A., Mattei C., Chameau P., Lawrence G., Colasante C., Kreger A.S., Dolly J.O. and Molgo, J. (2000). Trachynilysin mediates SNARE-dependent release of catecholamines from chromaffin cells via external and stored Ca2+. J. Cell Sci. 113:1119-25.
De Paiva A., Meunier F.A., Molgo J., Aoki R. and Dolly J.O., (1999). Basis of the functional repair of paralysed motor nerve endings: A bi-phasic switch in the loci of synaptic activity between nerve terminals and their botulinum toxin A-induced sprouts. Proc. Natl. Acad. Sci. U.S.A. 96: 3200-3205.
Davletov B.A., Meunier F.A., Ashton A.C., Matsushita H., Hirst W.D., Lelianova V.G., Wilkin G.P., Dolly J.O., and Ushkaryov Y.A. (1998). Vesicle exocytosis stimulated by alpha-latrotoxin is mediated by latrophilin and requires both external and stored Ca2+. EMBO J. 17: 3909-3920.
Reviews [top]
Osborne S.L., Meunier F.A. and Schiavo G. (2001). Phosphoinositides as key regulators of synaptic function. Neuron 32: 9-12.
Meunier F.A., Schiavo G., and Molgo, J. (2002). Botulinum neurotoxins: from paralysis to recovery of functional neuromuscular transmission. J. Physiol. (Paris) 96:105-113.
Foran P.G., Davletov B., and Meunier F.A. (2003). Getting muscles moving again after botulinum toxin: novel therapeutic challenges. Trends in Molecular Medicine 9: 9291-299.
Osborne S.L., Wen P.J. and Meunier F.A. (2006). Phosphoinositide regulation of neuroexocytosis: adding to the complexity. J Neurochem. 98:336-42.
Latham C.F. and Meunier F.A. (2007). Munc18a: Munc-y business in mediating exocytosis. Int J Biochem Cell Biol. 39:1576-81
Former members of the MDSF Laboratory [top]
Post Doctoral Scientists
- Dr Lotten Ragnarsson
- Dr Sonia Cavaignac
Doctoral Students
- Corinne Benakis “Granuphilin C2 domain”
- Lim Siew Joo (Tiff) (First class Hons)
- Wei Mei Guo (Mei) (First class Hons)
- Nhan Nguyen (First class Hons)
- Ivy Chun (Ivy)
- Warin Wirojanagud (First class Hons)
- Peter Wen (First class Hons, recipient of a UQ PhD fellowship)
- Dustin Proctor (First class Hons, recipient of a APA fellowship)
- Hao Ngoc (Lisa) Nguyen (First class Hons)
- Rachel Gormal
- Tim Rogers
- Jasmin Lee
Research Higher Degrees [top]
The Queensland Brain Institute is dedicated to providing world-class training opportunities for Research Higher Degree (postgraduate) students. All post-grad students are supervised by qualified research staff with national and international profiles in neuroscience.
A range of student projects are offered. Prospective students interested in working with QBI's researchers are welcome to contact the Lab Head directly for further information or visit QBI's website.
Students will join a stimulating interdisciplinary team of researchers that includes molecular biologists, stem cell biologists, electro-physiologists, neuropsychologists and mathematicians.
In November 2007, QBI will officially open its new $63 million seven-storey, research facility designed specifically for neuroscience, incorporating a unique range of equipment and cutting-edge technologies. The multi-disciplinary research environment and world-class facilities provide a unique experience for our research students.
Contact details [top]
Lab Head: Associate Professor Fred MeunierContact: f.meunier@uq.edu.au
Phone : (+61) 7 3346 6373