Signaling

Ronald Emeson, Ph.D.

Professor of Pharmacology

Joel G. Hardman Chair in Pharmacology

465 21st Avenue South, Nashville, TN, 37232-8548

Research Description

The research interests of our laboratory focus on the cellular and molecular processes underlying neuronal communication in normal and pathophysiologic disease states. Specifically, we are examining the molecular mechanisms involved in the editing of RNA transcripts encoding proteins critical for mammalian nervous system function. RNA editing is a post-transcriptional modification in which specific adenosine residues in pre-messenger RNAs are converted to inosine (A-to-I editing) by double-stranded RNA-specific adenosine deaminases (ADARs). As a result of these deamination events, the coding potential of RNAs can be subtly altered to change as little as a single amino acid residue in resultant products to generate protein isoforms with distinct functional properties.

Our current research efforts focus upon the physiological importance of RNA editing for transcripts encoding the 2C-subtype of serotonin receptor (5HT2C), a member of the Shaker-family of voltage-gated potassium channels (Kv1.1) and calcium-dependent activator protein for secretion 1 (CAPS1), a protein involved in the fusion of synaptic vesicles to the pre-synaptic membrane to promote neurotransmitter release. These studies take advantage of heterologous expression systems to assess the functional differences between protein isoforms encoded by edited and non-edited transcripts and subsequently lead to the generation of mutant mouse model systems where we can limit expression to a single protein isoform. For example, mutant mice solely expressing the non-edited form of the 5HT2C receptor demonstrate deficits in maternal behavior, whereas animals solely expressing the fully-edited isoform have a number of phenotypic alterations characteristic of human Prader-Willi syndrome. The long-term goal of the proposed research is to understand the mechanism(s) underlying the regulation of RNA editing and to define how such RNA processing events may contribute to functional protein diversity and dysfunction in the nervous system.

Selected Publications