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MICHAEL KOELLE

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, study them biochemically, and determine the detailed mechanisms underlying neurotransmission. Using this approach, 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 G protein with this target protein. We plan to clone and analyze the many other signaling genes we have identified genetically that mediate neurotransmission.

Some of the same G protein machinery that mediates neurotransmitter signaling is also found in embryonic cells where it controls microtubule forces that position the mitotic spindle to one side of a mother cell during asymmetric cell divisions. Such asymmetric cell divisions allow stem cells and other types of embryonic blast cells to produce two daughter cells that differ from each other. We are also using genetic and biochemical experiments to investigate the mechanism of G protein control of asymmetric divisions.

Selected Publications
Chase, D.L., Pepper, J.S. and Koelle, M.R. Mechanism of extrasynaptic dopamine signaling in C. elegans. Nature Neurosci. 7, 1096-1103 (2004)

Hess, H.A., Röper J.C., Grill, S.W. and Koelle, M.R. RGS-7 completes a receptor-independent heterotrimeric G protein cycle to asymmetrically regulate mitotic spindle positioning in C. elegans. Cell 119, 209-218 (2004)

Jose, A.M. and Koelle, M.R. Domains, amino acid residues, and new isoforms of C. elegans diacyglycerol kinase DGK-1 important for terminating diacylglycerol signaling in vivo. J. Biol. Chem. 280, 2730-2736 (2005)

Palmitessa, A., Hess, H.A., Bany, I.A., Kim, Y.M., Koelle, M.R. and Benovic, J.L. Caenorhabditus elegans arrestin regulates neural G protein signaling and olfactory adaptation and recovery. J. Biol. Chem. 280, 24649-24662 (2005)

Jose, A.M., Bany, I.A., Chase, D.L. and Koelle, M.R. A specific subset of TRPV channel subunits function as mixed heteromers to promote neurotransmitter release. Submitted (2006)

Last Updated 12-18-06