Robert L. Rosenberg, PhD
Professor
Director, Curriculum in Neurobiology
Joint appointment in Pharmacology

Education:

AB, Oberlin College, 1977
PhD, Yale University, 1985

Molecular mechanisms of activation of ion channels

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Our research is focused on the molecular mechanisms of activation of neuronal nicotinic acetylcholine receptors. These receptors are essential for normal synaptic activity in the brain. They are the target for nicotine, so they are an important component in nicotine addiction. Abnormalities of cholinergic neurotransmission are important in Alzheimer's disease, schizophrenia, epilepsy, and other neurological disorders. We are testing the hypothesis that ligand-driven conformational changes during activation include both subunit rotation and intrasubunit movements of a specific beta-sheet.  To characterize these conformational changes, we use cysteine mutagenesis, analysis of chemical modification rates, and electrophysiological approaches to characterize the functional properties of cloned receptors. We use a molecular model of the ligand-binding domain of the receptors to guide our mutagenesis and to help us interpret the results.

Recent Publications

McLaughlin JT, Fu J, Sproul AD, Rosenberg RL. (2006) Role of the outer beta-sheet in divalent cation modulation of alpha7 nicotinic receptors. Mol Pharmacol 70(1): 16-22.

Olesky, M., Zhao, S., Rosenberg, R.L., and Nicholas, R.A. (2006) Porin-mediated antibiotic resistance in Neisseria gonorrhoeae: Ion, solute, and antibiotic permeation through PIB proteins with penB mutations. J Bacteriol 188(7):2300-8.

Lyford, L.K., Sproul A.D., Eddins, D., McLaughlin, J.T., and Rosenberg, R.L. (2003) Agonist-dependent conformational changes in the extracellular domain of a 7 nicotinic ACh receptors. Mol Pharmacol 64(3):650-658.

Eddins, D.E., Sproul, A.D., Lyford, L.K., McLaughlin, J.T., and Rosenberg, R.L. (2002) Glutamate 172, essential for modulation of L247T alpha7 ACh receptors by Ca²⁺, lines the extracellular vestibule. Am J Physiol (Cell Physiol) 283(5):C1454-C1460.

Lyford, L.K., Lee J.W., and Rosenberg, R.L. (2002) Low affinity Ca²⁺ and Ba²⁺ binding sites in the pore of α7 nicotinic acetylcholine receptors. Biochim. Biophys. Acta 1559, 69-78.

Lyford, L.K., Eddins, D., Lee, J.W., Desai, S.A., and Rosenberg , R.L. (2002) Permeant but not impermeant divalent cations enhance the potency and efficacy of ACh and DHbE on non-desensitizing a7 nAChRs. Am. J. Physiol. (Cell Physiol.) 282(4):C796-804.