The sense of smell plays a key role in the determination of behaviour in all vertebrates, including man. Olfaction is important for feeding, avoidance of dangers and various aspects of social communications such as kin recognition and mating. The neurophysiology and neuroanatomy of the olfactory pathway are well known, but an understanding of its molecular mechanism is still lacking. Our recent development of a well defined preparation of isolated frog olfactory cilia may be helpful in this respect. The cilia are membrane extensions of the chemosensory neurones, and are believed to contain the molecular apparatus of olfaction. In isolation they provide an ideal system for biochemical studies of sensory reception and transduction. The proposed research centers on two proteins identified by us as specific to olfactory cilia: 1) the glycoprotein gp95, the only major integral membrane protein of these sensory organelles, and one which fulfills many criteria for being olfactory receptor; 2) olfactory G-protein, a possible homologue of signal-transducing proteins that play a key role in vision, as well as in neurotransmitter and hormone reception. Evidence will be sought for the role of these proteins in olfaction. This will be done 1) by investigating the effect of monoclonal antibodies against gp95 and other ciliary surface proteins on olfactory responses in-vivo and in-vitro. 2) by monitoring protein phosphorylation in olfactory cilia, a reaction that has been found to be involved in the function of many other membrane receptors. 3) by studying the properties of the putatively identified olfactory G-protein, and probing its interaction with gp95 and other ciliary glycoproteins that may be candidate receptor molecules. 4) by studying the polypeptide heterogeneity of gp95, using amino acid sequence analysis. This is aimed at testing the hypothesis that olfactory receptor molecules form a multi-gene family evolved to recognize diverse chemical stimuli.
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