The serotonin type 3 (5-HT3) receptor is a multi-subunit ligand-gated ion channel. It is crucial for numerous cognitive and physiological processes. Antagonists of the 5-HT3 receptor are effectively used to treat schizophrenia and generalized anxiety disorder. Thus, understanding the regulation of this receptor is vital for developing treatments for mental illness. Little, however, is known about the expression and regulation of this receptor. Based on studies of related neurotransmitter receptors it is hypothesized that N-glycosylation is necessary for proper 5-HT3 receptor function. Additionally, it is suggested that 5-HT3 receptors interact directly with at least one other neurotransmitter receptor to regulate intracellular receptor trafficking and function. The role of N-glycosylation in 5-HT3 receptor function will be determined using N-glycosylation-deficient mutant receptors to identify the N-glycosylation sites important for ligand-binding and surface trafficking. To identify direct receptor-receptor interactions immunocytochemical, immunoprecipitation and blot overlay analyses will be performed. Finally, a neuronal culture system will be developed with which to analyze the way neurotransmitter receptor expression and function may be regulated in vivo. These studies will further the understanding of the serotonergic system, allowing the development of novel therapeutic agents to treat schizophrenia and other mental disorders.
| Quirk, Phillip L; Siegel, Ruth E (2005) The serotonin type 3A receptor facilitates luteinizing hormone release and LHbeta promoter activity in immortalized pituitary gonadotropes. Endocrine 27:37-43 |
| Quirk, Phillip L; Rao, Suma; Roth, Bryan L et al. (2004) Three putative N-glycosylation sites within the murine 5-HT3A receptor sequence affect plasma membrane targeting, ligand binding, and calcium influx in heterologous mammalian cells. J Neurosci Res 77:498-506 |
