Mixture interactions at mammalian olfactory receptors are dependent on the cellular environment.

Mixture interactions at mammalian olfactory receptors are dependent on the cellular environment.
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DOI:
10.1038/s41598-021-88601-0
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发表时间:
2021-04-29
期刊:
影响因子:
4.6
通讯作者:
Ukhanov K
Ukhanov K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Corey EA;Zolotukhin S;Ache BW;Ukhanov K

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哺乳动物嗅觉受体(ORs)的功能表征仍然是最终理解嗅觉密码的主要挑战。在这里,我们比较了小鼠Olfr73异位表达的嗅觉感觉神经元使用AAV基因传递在体内和在体外细胞培养中表达的反应。异位表达的Olfr 73的激动剂的响应动力学和浓度依赖性与内源性Olfr 73报道的那些相似,然而先前报道的其同源激动剂和几种拮抗剂之间的拮抗作用在体内没有复制。表达的OR在体外重现的拮抗作用报告短的气味脉冲,但不为长期的气味暴露。我们的研究结果表明,无论是细胞环境和刺激动力学形状的Olfr73的功能,并认为,在“天然”条件下,而不是在体外,表征OR,提供了一个更相关的了解配体OR相互作用。
Functional characterization of mammalian olfactory receptors (ORs) remains a major challenge to ultimately understanding the olfactory code. Here, we compare the responses of the mouse Olfr73 ectopically expressed in olfactory sensory neurons using AAV gene delivery in vivo and expressed in vitro in cell culture. The response dynamics and concentration-dependence of agonists for the ectopically expressed Olfr73 were similar to those reported for the endogenous Olfr73, however the antagonism previously reported between its cognate agonist and several antagonists was not replicated in vivo. Expressing the OR in vitro reproduced the antagonism reported for short odor pulses, but not for prolonged odor exposure. Our findings suggest that both the cellular environment and the stimulus dynamics shape the functionality of Olfr73 and argue that characterizing ORs in ‘native’ conditions, rather than in vitro, provides a more relevant understanding of ligand-OR interactions.
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