Illumination of TAAR2 Location, Function and Regulators

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Project Summary This proposal is prepared in response to RFA-RM-22-024, which invites “Pilot projects investigating understudied G protein-coupled receptors, ion channels and protein kinases”. We choose to study trace amine associated receptor 2 (TAAR2) which is an understudied GPCR and an IDG-eligible protein under this FOA. TAAR2 was discovered as a GPCR in 2001 and has been speculated to be involved in neurological and psychiatric diseases; however, little progress has been made towards understanding the action of TAAR2 and creating experimental tools. To address the current knowledge gap, we will investigate TAAR2 cellular and subcellular localization, trafficking and signal transduction using human SH-SY5Y cells and rodent brains. Further, this proposal will also apply CRISPR/Cas9-mediated homology-directed repair mechanism to tag Taar2 gene in SH-SY5Y cells so that TAAR2-interacting protein network can be revealed through proteomics. Knowledge learned and products generated from this proposal will add value to the IDG program and importantly, lay ground work for future investigation of TAAR2 in animal models of human diseases.