Activation of Trace Amine-Associated Receptor 1 (TAAR1) by Zinc Binding in Mutated Orthosteric Site
Trace amine-associated receptor 1 (TAAR1) is a promising drug target for drug addiction and schizophrenia. It plays a significant role in neurotransmitter regulation in the central nervous system, specifically the dopaminergic and serotonergic systems. Creating mutants of TAAR1 allows for its activation pathway and overall function to be better understood compared to wildtype TAAR1. The single amino acid substitution for the I290 residue was utilized in the TAAR1 zinc binding orthosteric site to assess a change in binding affinities for potential drugs. This activation was observable in Xenopus laevis oocytes during two-electrode voltage clamp electrophysiology in a solution of zinc ions, which open G protein-gated inwardly rectifying potassium channels (GIRK) to allow for the measurement of ion flow across the membrane.
Keywords: TAAR1, B2AR, Mutagenesis, Drug addiction, Electrophysiology
Topic(s):Biochemistry and Molecular Biology
Presentation Type: Oral Presentation
Session: 108-2
Location: MG 1000
Time: 8:45