Biochemistry; Biophysics; Molecular Biology; Neurobiology; Serotonin; Caenorhabditis elegans; Neurotransmitter Agents; RGS Proteins
We study the mechanism of signaling by neurotransmitters, the molecules neurons use to communicate with each other. We first identify and study behavioral mutants of the nematode C. elegans in which neurotransmitter signaling is defective. By cloning the genes defined by the 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 the G proteins that mediate much of the signaling in the brain. One current project focuses how signaling by the neurotransmitter GABA is regulated to reduce neural activity enough to prevent seizures but not so much as to prevent any activity. Another project seeks to uncover the basic mechanisms of signaling by the neurotransmitter serotonin, defects in which are thought to underlie depression in humans.
Specialized Terms: C. Elegans; G Protein; Neurotransmission; RGS Protein; Serotonin; Molecular Genetics; Neurobiology; Neurotransmitters; Proteins and Macromolecules; Receptors
- Bellemer, A., Hirata, T., Romer,o M.F., and Koelle, M.R. (2011). Two types of chloride transporters are required for GABA(A) receptor-mediated inhibition in C. elegans. EMBO J. 30, 1852-1863.
- Hofler, C., and Koelle, M.R. (2011). AGS-3 alters Caenorhabditis elegans behavior after food deprivation via RIC-8 activation of the neural G protein G alpha(o). J. Neurosci. 31, 11553-11562.
- Porter, M.Y., and Koelle, M.R. (2009). RSBP-1 is a membrane targeting subunit required by the Gaq-specific but not the Gao-specific R7 Regulator of G protein Signaling in Caenorhabditis elegans. Mol. Biol. Cell, in press.
- Tanis, J.E., Bellemer, A., Moresco, J.J., Forbush, B., and Koelle, M.R. (2009). The potassium chloride cotransporter KCC-2 coordinates development of inhibitory neurotransmission and synapse structure in C. elegans. J. Neurosci. 29, 9943-9954.
- Jose, A.M., Bany, I.A., Chase, D.L., and Koelle, M.R. (2007). A specific subset of TRPV channel subunits in Caenorhabditis elegans endocrine cells function as mixed heteromers to promote neurotransmitter release. Genetics 175:93-105.
- 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)
- 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. 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)
- Hess, H.A., Röper, J.C., Grill, S.W., and Koelle, M.R. (2004). RGS-7 completes a receptor-independent heterotrimeric G protein cycle to asymmetrically regulate mitotic spindle positioning in C. elegans. Cell 119:209-218.