The sense of smell plays an important role in vertebrate behavior. In man it is crucial for the assessment of food quality and the avoidance of harmful substances. Olfaction also underlies many aspects to human social interactions. While several components of the molecular olfactory mechanism distal to the receptors have been extensively studied, the protein receptors themselves remain elusive. Their understanding constitutes a major challenge for olfactory research. The present proposal centers on the identification, isolation and molecular cloning of olfactory receptor proteins. The proposed research relies strongly on the knowledge of post-receptor components which was obtained during the first three years of research supported by this grant. Such information includes the identification and study of functional membrane proteins in olfactory cilia, namely olfactory GTP-binding protein (G-protein), odorant-sensitive adenylate cyclase, the cilia-specific glycoprotein gp95 (a receptor candidate), and phosphoproteins pp24 and pp26. The proposed research includes the following lines of investigation: a) Molecular cloning of the frog ciliary receptor candidate gp95 as well as its putative mammalian counterpart gp56. b) Molecular cloning of other receptor candidates, utilizing the establishment structural homology among members of the G-protein- activating receptor superfamily. c) Investigation of the phosphorylation of candidate receptor proteins possibly related to chemosensory adaptation. d) Study of the interaction of olfactory transduction components, GTP-binding proteins and adenylate cyclase, with candidate olfactory receptors.
