Dataset Information

Modification of the response of olfactory receptors to acetophenone by CYP1a2.

ABSTRACT: Olfaction is mediated by the binding of odorant molecules to olfactory receptors (ORs). There are numerous proteins in the nasal mucus, and they contribute to olfaction through various mechanisms. Cytochrome P450 (CYP) family members are known to be present in the olfactory epithelium and are thought to affect olfaction by enzymatic conversion of odorant molecules. In this study, we examined the effects of CYPs on the ligand responses of ORs in heterologous cells. Among the CYPs tested, co-expression of CYP1a2 significantly affected the responses of various ORs, including MOR161-2, to acetophenone. Conversion of acetophenone to methyl salicylate was observed in the medium of CYP1a2-expressing cells. MOR161-2-expressing cells exhibited significantly greater responses to methyl salicylate than to acetophenone. Finally, we analyzed the responses of olfactory neurons expressing MOR161-2 in vivo using the phosphorylated ribosomal protein S6 as a marker. MOR161-2 responded to both acetophenone and methyl salicylate in vivo. When the olfactory mucus was washed out by the injection of PBS to mouse nasal cavity, the response of MOR161-2 to acetophenone was reduced, while that to methyl salicylate did not change. Our data suggest that CYP1a2 affects OR activation by converting acetophenone to methyl salicylate.

SUBMITTER: Asakawa M

PROVIDER: S-EPMC5579037 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Modification of the response of olfactory receptors to acetophenone by CYP1a2.

Asakawa Masashi M Fukutani Yosuke Y Savangsuksa Aulaphan A Noguchi Keiich K Matsunami Hiroaki H Yohda Masafumi M

Scientific reports 20170831 1

Olfaction is mediated by the binding of odorant molecules to olfactory receptors (ORs). There are numerous proteins in the nasal mucus, and they contribute to olfaction through various mechanisms. Cytochrome P450 (CYP) family members are known to be present in the olfactory epithelium and are thought to affect olfaction by enzymatic conversion of odorant molecules. In this study, we examined the effects of CYPs on the ligand responses of ORs in heterologous cells. Among the CYPs tested, co-expre ...[more]

PMID: 28860658

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Project description:BackgroundEvolution has resulted in large repertoires of olfactory receptor (OR) genes, forming the largest gene families in mammalian genomes. Knowledge of the genetic diversity of olfactory receptors is essential if we are to understand the differences in olfactory sensory capability between individuals. Canine breeds constitute an attractive model system for such investigations.ResultsWe sequenced 109 OR genes considered representative of the whole OR canine repertoire, which consists of more than 800 genes, in a cohort of 48 dogs of six different breeds. SNP frequency showed the overall level of polymorphism to be high. However, the distribution of SNP was highly heterogeneous among OR genes. More than 50% of OR genes were found to harbour a large number of SNP, whereas the rest were devoid of SNP or only slightly polymorphic. Heterogeneity was also observed across breeds, with 25% of the SNP breed-specific. Linkage disequilibrium within OR genes and OR clusters suggested a gene conversion process, consistent with a mean level of polymorphism higher than that observed for introns and intergenic sequences. A large proportion (47%) of SNP induced amino-acid changes and the Ka/Ks ratio calculated for all alleles with a complete ORF indicated a low selective constraint with respect to the high level of redundancy of the olfactory combinatory code and an ongoing pseudogenisation process, which affects dog breeds differently.ConclusionOur demonstration of a high overall level of polymorphism, likely to modify the ligand-binding capacity of receptors distributed differently within the six breeds tested, is the first step towards understanding why Labrador Retrievers and German Shepherd Dogs have a much greater potential for use as sniffer dogs than Pekingese dogs or Greyhounds. Furthermore, the heterogeneity in OR polymorphism observed raises questions as to why, in a context in which most OR genes are highly polymorphic, a subset of these genes is not? This phenomenon may be related to the nature of their ligands and their importance in everyday life.

Dataset Information

Modification of the response of olfactory receptors to acetophenone by CYP1a2.

Publications

Modification of the response of olfactory receptors to acetophenone by CYP1a2.

Similar Datasets

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