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Michael Koelle
Associate Professor of Molecular Biophysics & Biochemistry
- B.S. University of Washington, 1986
- Ph.D. Stanford University, 1992
Research Interests:
- G protein signaling in the C. elegans nervous system
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Neurotransmission through G protein coupled receptors modulates
the activities of neurons and may underlie some forms of memory
in higher organisms. We identify and study behavioral mutants
of the nematode C. elegans in which this form of neurotransmitter
signaling is defective. By cloning the genes defined by these
mutations we can identify the molecules responsible for signaling.
The lab has also expressed and purified recombinant forms of the
signaling proteins we identified genetically and we are using
these proteins to investigate the biochemical mechanisms underlying
neural signaling.
Using these approaches, we discovered a large family of Regulators
of G Protein Signaling (RGS proteins) that directly inactivate
G proteins. We are carrying out both biochemical and genetic studies
of RGS proteins to find out how and why cells use these regulators.
Our genetic experiments also identified a protein that may be
the direct target activated by the major neural G protein. We
are currently analyzing the interactions of the purified G protein
with this purified target protein. We plan to clone and analyze
the many other signaling genes we have identified genetically
that mediate neurotransmission.
The 302 neurons of C. elegans (diagrammed here as black
circles) make ~7000 synapses, and the position of each neuron
and synapse is known. The two HSN motor neurons are required for
egg-laying behavior: if they are ablated using a laser microbeam,
the resulting animals can no longer lay eggs. Wild-type animals
increase or decrease their frequency of egg-laying behavior depending
on the presence or absence of food in their environment. By isolating
mutants that disrupt this regulation we have identified genes
that may control the activity level of the HSN neurons.
- Representative Publications:
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- Genetics. 2007 Jan;175(1):93-105.
- A specific subset of transient receptor potential vanilloid-type channel subunits in Caenorhabditis elegans endocrine cells function as mixed heteromers to promote neurotransmitter release.
- Jose A. M., Bany I. A., Chase D. L., Koelle M. R.
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- J.
Biol Chem. 2005 Jan 28;280(4):2730-6.
- Domains, amino acid residues, and new isoforms of C. elegans
diacylglycerol kinase DGK-1 important for terminating diacylglycerol
signaling in vivo.
- Jose A. M., Koelle M. R.
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- Cell.
2004 Oct 15; 119(2):209-18.
- RGS-7 completes a Receptor-Independent Heterotrimeric G-protein
Cycle to Asymmetrically Regulate Mitotic Spindle Positioning
in C. elegans.
- Hess H. A., Roper J. C., Grill S.W., Koelle M. R.
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- Nat
Neurosci. 2004 Oct ;7(10):1096-103.
- Mechanism of extrasynaptic dopamine signaling in Caenorhabditis
elegans
- Chase D. L., Pepper J. S., Koelle M. R.
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- J
Neurosci. 2004 Sep 29;24(39):8522-30.
- Activation of EGL-47, a Galphao-coupled receptor, inhibits
function of hermaphrodite-specific motor neurons to regulate
Caenorhabditis elegans egg-laying behavior
- Moresco J. J., Koelle M. R.
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- Methods Enzymol. 2004; 389:305-20.
- Genetic analysis of RGS Protein Function in Caenorhabditis
elegans
- Chase D. L., Koelle M. R.
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- J
Neurosci. 2003 Sep 3;23(22):8060-9.
- Genetic and cellular basis for acetylcholine inhibition of
Caenorhabditis elegans egg-laying
behavior.
- Bany I. A., Dong M. Q., Koelle M. R.
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- J
Biol Chem. 2002 Dec 6;277(49):47004-13.
- An N-terminal Region of Caenorhabditis elegans RGS Proteins
EGL-10 and EAT-16 Directs Inhibition of Galpha oVersus Galpha
q Signaling.
- Patikoglou, G. A. and Koelle, M. R.
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- Current
Biology. 2001. 11: 222-231.
Two RGS proteins that inhibit Gao
and Gaq signaling in C. elegans neurons
require a Gß5-like subunit for function.
Chase, D.L., Patikoglou, G.A, and Koelle, M.R.
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- Genes
Dev. 2000 Aug 15;14(16):2003-14.
Multiple RGS proteins alter neural G protein signaling to allow
C. elegans to rapidly change behavior when fed.
Dong M-Q, Chase D, Patikoglou GA, Koelle MR.
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- Curr Opin Cell Biol.
1997 Apr;9(2):143-7. Review.
A new family of G-protein regulators - the RGS proteins.
Koelle MR
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- Cell 84: 115-125 1996
EGL-10 regulates G protein signaling in the C. elegans nervous
system and shares a conserved domain with many mammalian proteins.
Koelle MR, Horvitz HR
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