Odorant-sensitive adenylate cyclase may mediate olfactory reception

Abstract

The mechanism of the sense of smell has long been a subject for theory and speculation. More recently, the notion of odorant recognition by stereospecific protein receptors has gained wide acceptance, but the receptor molecules remained elusive. The recognition molecules are believed to be quite diverse, which would partly explain the unusual difficulties encountered in their isolation by conventional ligand-binding techniques. An alternative approach would be to probe the receptors through transductory components that may be common to all receptor types. Here we report the identification of one such transductory molecular component. This is an odorant-sensitive adenylate cyclase, present in very large concentrations in isolated dendritic membranes of olfactory sensory neurones. Odorant activation of the enzyme is ligand and tissue specific, and occurs only in the presence of GTP, suggesting the involvement of receptor(s) coupled to a guanine nucleotide binding protein (G-protein). The olfactory G-protein is independently identified by labelling with bacterial toxins, and found to be similar to stimulatory G-proteins in other systems. Our results suggest a role for cyclic nucleotides in olfactory transduction, and point to a molecular analogy between olfaction and visual, hormone and neurotransmitter reception. Most importantly, the present findings reveal new ways to identify and isolate olfactory receptor proteins.

Bestrophin-2 is a candidate calcium-activated chloride channel involved in olfactory transduction

“…For Western blot, membrane fractions enriched in olfactory cilia from OSNs were obtained with the calcium-shock method according to ref. 44 …”

Contribution of the receptor guanylyl cyclase GC-D to chemosensory function in the olfactory epithelium

“…Upon ligand binding, odorant receptors activate the G protein G␣ olf , which stimulates type III adenylyl cyclase to increase intracellular levels of cAMP (4)(5)(6)(7)(8)(9). This second messenger then directly opens cAMPsensitive, cyclic nucleotide-gated (CNG) channels in the plasma membrane, resulting in the initial depolarization of the cell (3,4).…”

Odorants Stimulate the ERK/Mitogen-activated Protein Kinase Pathway and Activate cAMP-response Element-mediated Transcription in Olfactory Sensory Neurons

“…These features of the sensory apparatus suggest that the initial encoding of odorant features is combinatorial, integrating spatio-temporal differences in receptor activation throughout the epithelium as well as differences in odorant concentration (6). Although each of the perhaps ϳ1000 individual odorant receptors has unique specificity for ligand binding, most if not all olfactory signaling is mediated through cAMP (7)(8)(9)(10). Odorant receptor activation increases intracellular cAMP via an interaction with G olf or G s and adenylyl cyclase activation.…”