Investigation of the nuclear localization of the βγ subunit of heterotrimeric G proteins

In addition to established functions at the plasma membrane, G protein coupled receptor (GPCR)‐initiated pathways directly impact the functions of internal organelles, including the nucleus. Probing the impact of nuclear GPCR activity on cellular physiology promises to elucidate connections between GPCRs and neoplastic diseases, which integrally involve aberrant gene regulation. We are focusing on roles for Gβγ in the mechanisms of transcriptional regulation observed upon stimulation of specific nuclearized GPCRs. Previous research has demonstrated both the physical presence of Gβγ in the nucleus and downstream effects consistent with signaling through nuclear Gβγ. Remaining to be established is the mechanism by which Gβγ arrives in the nucleus. Is Gβγ a consistent resident of the nucleus in some population of cells or does it migrate to the nucleus downstream of a signal? We propose that in certain cases Gβγ enters the nucleus simultaneously as a GPCR moves into this organelle. To test this hypothesis, we will present microscopic and cellular dissection data investigating the time and temperature‐dependent sub‐cellular localization of Gβγ in cultured cell models in which the Gi‐coupled sphingosine 1‐phosphate receptor 1 (S1P 1 ) localizes to the nucleus upon stimulation. These results will inform future and concurrent studies into downstream effects of nuclear Gβγ activation.