Heterotrimeric G Protein Subunit G gamma 13 Is Critical to Olfaction

The activation of G-protein-coupled olfactory receptors on the olfactory sensory neurons (OSNs) triggers a signaling cascade, which is mediated by a heterotrimeric G-protein consisting of alpha, beta, and gamma subunits. Although its alpha subunit, G alpha olf, has been identified and well characterized, the identities of its beta and gamma subunits and their function in olfactory signal transduction, however, have not been well established yet. We, and others, have found the expression of G gamma 13 in the olfactory epithelium, particularly in the cilia of the OSNs. In this study, we generated a conditional gene knock-out mouse line to specifically nullify G gamma 13 expression in the olfactory marker protein-expressing OSNs. Immunohistochemical and Western blot results showed that G gamma 13 subunit was indeed eliminated in the mutant mice's olfactory epithelium. Intriguingly, G alpha olf, beta 1 subunits, Ric-8B and CEP290 proteins, were also absent in the epithelium whereas the presence of the effector enzyme adenylyl cyclase III remained largely unaltered. Electro-olfactogram studies showed that the mutant animals had greatly reduced responses to a battery of odorants including three presumable pheromones. Behavioral tests indicated that the mutant mice had a remarkably reduced ability to perform an odor-guided search task although their motivation and agility seemed normal. Our results indicate that G alpha olf exclusively forms a functional heterotrimeric G-protein with G beta 1 and G gamma 13 in OSNs, mediating olfactory signal transduction. The identification of the olfactory G-protein's beta gamma moiety has provided a novel approach to understanding the feedback regulation of olfactory signal transduction pathways as well as the control of subcellular structures of OSNs.