Molecular Neuropharmacology Section - Division of Intramural Research
David R. Sibley, Ph.D., Senior Investigator
Dr. Sibley received his B.S. degree in Biology from San Diego State University and his Ph.D. in Physiology/Pharmacology from the University of California, San Diego where he worked with Ian Creese studying the ligand binding properties of dopamine receptors. He subsequently carried out postdoctoral work with Robert Lefkowitz at Duke University where he characterized adrenergic receptor regulatory mechanisms. Dr. Sibley moved to the NINDS in 1987 and was appointed Chief of the Molecular Neuropharmacology Section in 1992. His laboratory is currently investigating the molecular, cellular and biochemical properties of dopamine receptors and their role in neuronal signaling.
, B.S., Graduate Student
, Ph.D., Postdoctoral Fellow
, B.S., Postbaccalaureate IRTA
R. Benjamin Free
, Ph.D., Staff Scientist
Julia A. Meade
, B.A., Postbaccalaureate IRTA
, Ph.D., Postdoctoral Fellow
, B.S., Laboratory Manager
The long-term goal of the Molecular Neuropharmacology Section is the characterization of neurotransmitter receptor-mediated information transduction, and its regulation, across neuronal membranes. The primary model systems under investigation are those neurotransmitter receptors that are linked to their signal transduction pathways via guanine nucleotide binding regulatory (G) proteins with specific emphasis on dopamine receptor subtypes. Specific G proteins have been shown to link these receptors to the activation and inhibition of various nucleotide cyclases, phospholipases, and several ion channels. In order to characterize these receptors at the biochemical and molecular levels and study their regulation, there are several ongoing interrelated lines of research. Such projects include investigating receptor structure/function/pharmacology relationships, receptor-effector coupling mechanisms, G protein interactions, and molecular mechanisms of receptor desensitization and intracellular trafficking. We are also interested in using high throughput screening approaches to develop novel ligands for modulating dopamine receptor expression and signaling. These ligands may prove useful in the development of novel pharmacological therapies for treating numerous neurological and psychiatric disorders associated with aberrant dopaminergic signaling.
Selected Recent Publications
Rex, E., Rankin, M.L., Yang, Y., Lu, Q., Gerfen, C.R., and Sibley, D.R.
Identification of RanBP9/10 as interacting partners for protein kinase Cs Î³/Î´ and the D1 dopamine receptor: regulation of PKC-mediated receptor phosphorylation, Molecular Pharmacology, 2010, vol. 78, pp. 69-80. Full Text/Abstract
Rankin, M.L., and Sibley, D.R.
Consitutive phosphorylation by protein kinase C regulates D1 dopamine receptor signaling, Journal of Neurochemistry, 2010, vol. 115, pp. 1655-1667. Full Text/Abstract
Namkung, Y., Dipace, C., Javitch, J.A., and Sibley, D.R.
G protein-coupled receptor kinase-mediated phosphorylation mediates post-endocytic trafficking of the D2 dopamine receptor, Journal of Biological Chemistry, 2009, vol. 284, pp. 15038-15051. Full Text/Abstract
Namkung, Y., Dipace, C., Urizar, U., Javitch, J.A., and Sibley, D.R.
G protein-coupled receptor kinase-2 constitutively regulates D2 receptor expression and signaling independent of receptor phosphorylation, Journal of Biological Chemistry, 2009, vol. 284, pp. 34103-34115. Full Text/Abstract
Rex, E.B., Rankin, M.L., Ariano, M.A., and Sibley, D.R.
Ethanol Regulation of D1 Dopamine Receptor Signaling is Mediated by Protein Kinase C in an Isozyme-Specific Fashion, Neuropsychopharmacology, 2008, vol. 32, pp. 2900-2911. Full Text/Abstract
Hazelwood, L.A., Free, B.F., Cabrera, D.M., Skinbjerb, M., and Sibley, D.R.
Reciprocal modulation of function between the D1 and D2 dopamine receptors and the Na+, K+-ATPase, Journal of Biological Chemistry, 2008, vol. 283, pp. 36441-36453. Full Text/Abstract
Kim, O.J., Ariano, M.A., Namkung, Y., Marinec, P., Kim, E., Han, J., and David R. Sibley
D2 dopamine receptor expression and trafficking is regulated through direct interactions with ZIP, Journal of Neurochemistry, 2008, vol. 106, pp. 83-95. Full Text/Abstract
Free, R.B., Hazelwood, L.A., Namkung, Y., Cabrera, D.M., Spalding, H.N., Rankin, M.L., and Sibley, D.R.,
D1 and D2 Dopamine Receptor Expression is Regulated by Direct Interaction with the Chaperone Protein Calnexin, Journal of Biological Chemistry, 2007, vol. 282, pp. 2185-21300. Full Text/Abstract
Selected Earlier Publications