Low signaling efficiency from receptor to effector in olfactory transduction: A quantified ligand-triggered GPCR pathway

Abstract

G protein-coupled receptor (GPCR) signaling is ubiquitous. As an archetype of this signaling motif, rod phototransduction has provided many fundamental, quantitative details, including a dogma that one active GPCR molecule activates a substantial number of downstream G protein/enzyme effector complexes. However, rod phototransduction is light-activated, whereas GPCR pathways are predominantly ligand-activated. Here, we report a detailed study of the ligand-triggered GPCR pathway in mammalian olfactory transduction, finding that an odorant-receptor molecule when (one-time) complexed with its most effective odorants produces on average much less than one downstream effector. Further experiments gave a nominal success probability of tentatively ∼1024 (more conservatively, ∼1022 to ∼1025). This picture is potentially more generally representative of GPCR signaling than is rod phototransduction, constituting a paradigm shift.