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After
completing undergraduate work in Biology at Washington University
in St. Louis, Michael Kavanaugh received his Ph.D. in Biochemistry
from OHSU in 1987. He pursued a postdoctoral fellowship at the Vollum
Institute and joined the Vollum faculty in 1993. Kavanaugh joined
the University of Montana in January 2003. Mike was promoted to CSFN Director in April 2008.
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INTERESTS OF THE KAVANAUGH LABORATORY
Research
in the Kavanaugh laboratory focuses on neurotransmitter transporters,
membrane proteins involved in reuptake and signaling in neurons.
We integrate electrophysiological and molecular biological approaches
in this work. Transporters and channels are studied using techniques
including voltage-clamp recording, radiotracer flux measurement,
and fluorescent labeling. The behavior of these molecules is studied
in heterologous expression systems as well as native tissues including
brain slice and cultured neurons and astrocytes.
Understanding
the biophysical properties of neurotransmitter transporters is necessary
for understanding their physiological roles. In the brain, transporters
mediate the reuptake of neurotransmitter after its release from
the presynaptic terminal. We are particularly interested in the
structural and functional properties of transporters for glutamate,
the major central nervous system excitatory neurotransmitter. We
are investigating the molecular mechanisms involved in translocating
glutamate across the cell membrane by studying ion fluxes and the
effects of mutations on transport properties. We are also applying
new fluorescent techniques to the study of transporter function.
Studies of other transport systems involved in CNS function are
also ongoing and include transporters for glutamine and monoamines.
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SELECTED PUBLICATIONS
Kavanaugh,
M.P. (2004) Accessing a transporter structure. Nature 431:752-3.
Larsson,
H.P., Tzingounis, A.V., Koch, H.P., and Kavanaugh, M.P. (2004) Fluorometric
measurements of conformational changes in glutamate transporters.
Proc. Nat. Acad. Sci.,101:3951-56
Chaudhry
FA, Schmitz D, Reimer RJ, Larsson P, Gray AT, Nicoll R, Kavanaugh
M, Edwards RH. (2002) Glutamine uptake by neurons: interaction of
protons with system A transporters. J Neurosci. 22 62-72.
Otis, T.S. and Kavanaugh, M.P. (2000) Isolation of current components
and partial reaction cycles in the glial glutamate transporter EAAT2.
J. Neurosci. 20:2749-57.
Otis TS and Kavanaugh MP. (1999) Glutamate transporters and their
contributions to excitatory synaptic transmission. Handbook of Exp.
Pharmacol. 141:419-440.
Eliasof S, Arriza JL, Leighton BH, Amara SG, Kavanaugh MP. (1998)
Localization and function of five glutamate transporters cloned
from the salamander retina. Vision Res. 38 1443-54.
Tzingounis AV, Lin CL, Rothstein JD, and Kavanaugh MP. (1998) Arachidonic
acid activates a proton current in the rat glutamate transporter
EAAT4. J. Biol. Chem. 273: 17315-17357.
Kavanaugh MP. (1998) Neurotransmitter transport: models in flux.
Proc Natl Acad Sci U S A. 95 12737-8.
Wadiche
JI and Kavanaugh MP. (1998) Macroscopic and microscopic properties
of a cloned glutamate transporter/chloride channel. J. Neurosci.
18:7650-7661.
Otis
TS, Kavanaugh MP, Jahr CE. (1997) Postsynaptic glutamate transport
at the climbing fiber-Purkinje cell synapse. Science. 277 1515-8.
Zerangue N, Kavanaugh MP. (1996) Flux coupling in a neuronal glutamate
transporter. Nature. 383 634-7.
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