MICHAEL C. WILSON, Ph.D.Professor |
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Education
and Honors:
1969, B.A., Biology, Hunter College, CUNY; 1971, Diploma in Epigenetics, University
of Edinburgh; 1976, Ph.D., Molecular Biology, University of Zurich; 1976-80,
Postdoctoral Fellow, Rockefeller University, New York; 1980-1996, Assistant
- Associate Member, The Scripps Research Institute, La Jolla, CA. 1976-78, NIH
Postdoctoral Fellow; 2003, A. Earl Walker Award
Research
Interests:
Ca++ regulated
exocytotic release of neurotransmitters provides for chemical signaling between
neurons and neuroendocrine cells and their postsynaptic target cells. Our laboratory
is interested in the regulation of neurotransmitter release, and its impact
on nervous system development and function, and how it contributes to behavior,
learning and memory. Our studies are focused on genetic manipulations of the
gene encoding SNAP-25, which together with integral membrane proteins syntaxin
and synaptobrevin/VAMP constitute the neural SNARE core machinery required for
Ca++-triggered
neuroexocytotic release of neurotransmitters. To better understand mechanisms
that underlie synaptic transmission, we have emphasized a molecular genetic
approach integrated with developmental, physiological and behavioral analyses.
Most recently, this includes developing homologous recombination knock-out and
knock-in mutations of the Snap25 gene in the mouse. Our studies have revealed
the role of neural SNARE complexes in promoting regulated action potential-dependent
and –independent modes of neurotransmitter release (“singing”
and “humming” by neurons) and its impact on nervous system development,
synapse formation and maturation. Current investigations are continuing to evaluate
the mechanisms responsible for change in the exocytotic machinery, Ca++-dependency
and efficacy of synaptic communication, and how they affect neural plasticity
required for learning and memory in these mutant mice.
Based on our early investigations of the SNAP-25 deficient mutant mouse Coloboma and more recently by genetic association studies in human populations, the SNAP25 gene has been considered as a potential susceptibility locus for attention-deficit/hyperactivity disorder (ADHD), the most prevalent neuropsychiatric disorder in children. Together with Drs. Don Partridge and Andrea Allan in the Neurosciences Department, we are evaluating the electrophysiological, pharmacological and behavioral consequences in mice that result from a deficiency of SNAP-25 expression together with prenatal nicotine exposure, a risk factor of maternal smoking during pregnancy for ADHD. By taking this multidisciplinary approach we hope to achieve a mechanistic understanding of the role of gene x environment interactions during the development of cognitive deficiencies and mental illness in humans.
Selected Publications:
Oyler, G.A., Higgins, G.A., Hart, R.A., Battenberg, E., Billingsley, M., Bloom, F.E. and Wilson, M.C. (1989) The identification of a novel synaptosomal associated protein, SNAP-25, differentially expressed by neuronal subpopulations. J.Cell. Biol. 109:3039-3052.
Steffensen, S.C., Wilson, M.C. and Henriksen, S.J. (1996) Coloboma contiguous gene deletion encompassing Snap alters synaptic plasticity. Synapse 22:281-289.
Hess, E.J., Collins, K.A. and Wilson, M.C. (1996) Mouse model of hyperkinesis implicates SNAP-25 in behavioral regulation. J. Neurosci. 16:3104-3111.
Raber, J., Mehta, P.P., Kreifeldt, M., Parson, L.H. Weiss, F., Bloom, F.E., and Wilson, M.C. (1997) Coloboma hyperactive mutant mice exhibit regional and transmitter-specific deficits in neurotransmission. J. Neurochem. 68:176-186.
Steffensen, S.C., Kreitfeldt, M., Henriksen, S.J. and Wilson, M.C. (1999) Transgenic rescue of SNAP-25 restores dopamine-modulated synaptic transmission in the coloboma mutant. Brain Res. 847: 186-195.
Wilson, M.C. (2000) Coloboma mouse mutant as an animal model of hyperkinesis and Attention-deficit hyperactivity disorder. Neuroscience & Biobehavioral Reviews 24: 51-57.
Washbourne, P. Cancino, V., Mathews, J.R., Graham, M.E., Burgoyne, R.D., and Wilson, M.C. (2001) The cysteines of SNAP-25 are required for SNARE disassembly and exocytosis, not for membrane trafficking. Biochem.J. 357: 625-34.
Washbourne, P., Thompson, P.M. Carta, M., Costa, E.T., Mathews, J.R., Lopez-Benditó, G., Molnár, Z., Becher, M.W., Valenzuela, C.F. Partridge, L.D., and Wilson M.C. (2002) Genetic ablation of the t-SNARE SNAP-25 distinguishes mechanisms of neuroexocytosis. Nature Neuroscience 5: 19-26.
Molnár, Z., López-Bendito, G., Small, J. Partridge, L.D., Blakemore, C. and Wilson, M.C. (2002) Normal development of the embryonic thalamocortical connectivity occurs in the absence of evoked synaptic activity. J. Neurosci. 22: 10313-10323.
Sørensen, J.B., Nagy, G., Varoqueaux, F., Nehring, R., Brose, N., Wilson, M.C., and Neher, E. (2003) Differential control of the releasable vesicle pools by SNAP-25 splice variants and SNAP-23. Cell 114: 75-86.
Bark, C., Bellinger, F.P., Kaushal, A., Mathews, J.R., Partridge, L.D., Wilson, M.C. (2004) Developmentally regulated switch in alternatively spliced SNAP-25 isoforms alters facilitation of synaptic transmission. J. Neurosci. 24: 8796-8805.
Fan, H. Leve, E.W., Scullin, C., Gabaldon, J., Tallant, D., Bunge, S., Boyle, T., Wilson, M.C., and Brinker, C.J. (2005) Surfactant-assisted synthesis of water-soluble and biocompatible semiconductor quantum dot-micelles, NanoLetters 5: 645-648.
Nagy, G., Milosevic, I., Fasshauer, D., Müller M., de Groot, B., Lang, T., Wilson, M.C. and Sørensen, J.B. (2005) Alternative splicing of SNAP-25 regulates secretion through non-conservative substitutions in the SNARE domain. Mol.Biol.Cell, 16, 5675-5685.
Tafoya, L.C.R. Mameli, M., Miyashita, T., Mathews, J.R., Guzowski, J.F., Valenzuela, C.F., and Wilson, M.C. (2006) Expression and function of the neural SNARE SNAP-25 as a universal SNARE component in GABAergic neurons, J. Neurosci., 30, 7826-7838.
Bronk, P., Deak, F., Wilson, M.C., Liu, X., Südhof, T.C., and Kavalali, E.T. (2007) Differential effects of SNAP-25 deletion on Ca 2+-dependent and Ca 2+-independent neurotransmission. J. Neurophysiology, 98, 794-806, PMID: 17553942.
Tafoya, LCR, Shuttleworth, C.W., Yanagawa, Y., Obata, K., Wilson, M. C. (2008) The t-SNARE SNAP-25 is required for action potential-dependent calcium signaling, but not constitutive neuroexocytosis in GABAergic and glutamatergic neurons. BMC Neuroscience, 9:105, PMID: 18959796
Mazelova, J., Ransom, R., Astuto-Gribble, L., Wilson, M.C. and Deretic, D. (2009) Syntaxin 3 and SNAP-25 pairing, regulated by omega-3 docosahexaenoic acid, and the sec6/8 tethering complex control fusion of the rhodopsin transport carriers and ciliary membrane expansion. J. Cell Sci. 122, 2003-2013. PMID: 19454479.
Corradini, I., Verderio, C., Sala, M., Wilson, M.C., and Matteoli, M. (2009) SNAP-25 in Neuropsychiatric Disorders. Ann.N.Y.Acad. Sci., 1152 93-99. PMID: 19161380, PMCID: PMC2706123
Postdoctoral position is now available to study molecular, developmental and physiological consequences of mouse mutants of the SNARE protein SNAP-25 that are deficit in neurotransmitter release.
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