Olfactory receptors: transduction, diversity, human psychophysics and genome analysis.

D. Lancet*, N. Ben-Arie, S. Cohen, U. Gat, R. Gross-Isseroff, S. Horn-Saban, M. Khen, H. Lehrach, M. Natochin, M. North

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

21 Scopus citations

Abstract

The emerging understanding of the molecular basis of olfactory mechanisms allows one to answer some long-standing questions regarding the complex recognition machinery involved. The ability of the olfactory system to detect chemicals at sub-nanomolar concentrations is explained by a plethora of amplification devices, including the coupling of receptors to second messenger generation through GTP-binding proteins. Specificity and selectivity may be understood in terms of a diverse repertoire of olfactory receptors of the seven-transmembrane-domain receptor superfamily, which are probably disposed on olfactory sensory neurons according to a clonal exclusion rule. Signal termination may be related to sets of biotransformation enzymes that process odorant molecules, as well as to receptor desensitization. Many of the underlying molecular components show specific expression in olfactory epithelium, with a well-orchestrated developmental sequence of emergence, possibly related to sensory neuronal function and connectivity requirements. A general model for molecular recognition in biological receptor repertoires allows a prediction of the number of olfactory receptors necessary to achieve efficient detection and sheds light on the analogy between the immune and olfactory systems. The molecular cloning and mapping of a human genomic olfactory receptor cluster on chromosome 17 provides insight into olfactory receptor diversity, polymorphism and evolution. Combined with future genotype-phenotype correlation, with particular reference to specific anosmia, as well as with computer-based molecular modelling, these studies may provide insight into the odorant specificity of olfactory receptors.

Original languageAmerican English
Pages (from-to)131-141; discussion 141-146
JournalCiba Foundation symposium
Volume179
StatePublished - 1993
Externally publishedYes

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