PI3Kγ-Dependent Signaling in Mouse Olfactory Receptor Neurons

摘要

Phosphatidylinositol 3-kinase (PI3K)-dependent signaling couples'to receptors for many different ligands in diverse cellular systems. Recent findings suggest that PBK-dependent signaling also mediates inhibition of odorant responses in rat olfactory receptor neurons (ORNs). Here, we present evidence that murine ORNs show PBK-dependent calcium responses to odorant stimulation, they express 2 G protein-coupled receptor (GPCR)-activated isoforms of PI3K, PBKβ and PI3Kγ, and they exhibit odorant-induced PI3K activity. These findings support our use of a transgenic mouse model to begin to investigate the mechanisms underlying PBK-mediated inhibition of odorant responses in mammalian ORNs. Mice deficient in PBKy, a class IB PI3K that is activated via GPCRs, lack detectable odorant-induced PBK activity in their olfactory epithelium and their ORNs are less sensitive to PBK inhibition. We conclude that odorant-dependent PBK signaling generalizes to the murine olfactory system and that PBKy plays a role in mediating inhibition of odorant responses in mammalian ORNs.