Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, 06269, USA.
MBF Bioscience, Williston, VT, 05495, USA.
Sci Rep. 2021 Oct 15;11(1):20530. doi: 10.1038/s41598-021-99910-9.
Members of the cytochrome p450 (CYP) enzyme family are abundantly expressed in insect olfactory tissues, where they are thought to act as Odorant Degrading Enzymes (ODEs). However, their contribution to olfactory signaling in vivo is poorly understood. This is due in part to the challenge of identifying which of the dozens of antennal-expressed CYPs might inactivate a given odorant. Here, we tested a high-throughput deorphanization strategy in Drosophila to identify CYPs that are transcriptionally induced by exposure to odorants. We discovered three CYPs selectively upregulated by geranyl acetate using transcriptional profiling. Although these CYPs are broadly expressed in the antenna in non-neuronal cells, electrophysiological recordings from CYP mutants did not reveal any changes in olfactory neuron responses to this odorant. Neurons were desensitized by pre-exposing flies to the odorant, but this effect was similar in CYP mutants. Together, our data suggest that the induction of a CYP gene by an odorant does not necessarily indicate a role for that CYP in neuronal responses to that odorant. We go on to show that some CYPs have highly restricted expression patterns in the antenna, and suggest that such CYPs may be useful candidates for further studies on olfactory CYP function.
细胞色素 P450(CYP)酶家族的成员在昆虫嗅觉组织中大量表达,被认为在其中作为气味降解酶(ODE)发挥作用。然而,它们在体内嗅觉信号传递中的作用仍知之甚少。部分原因是难以确定数十种触角表达的 CYP 中哪些可能使给定的气味失活。在这里,我们在果蝇中测试了一种高通量的去孤儿化策略,以鉴定对气味暴露具有转录诱导作用的 CYP。我们使用转录谱分析发现了三种被乙酸香叶酯选择性上调的 CYP。尽管这些 CYP 在非神经元细胞中在触角中广泛表达,但从 CYP 突变体中的电生理记录并未显示出嗅觉神经元对该气味的反应有任何变化。用气味预先暴露果蝇会使神经元脱敏,但在 CYP 突变体中也有类似的效果。总的来说,我们的数据表明,气味诱导 CYP 基因的表达并不一定表明该 CYP 在神经元对该气味的反应中起作用。我们接着表明,一些 CYP 在触角中的表达模式受到高度限制,并表明这些 CYP 可能是进一步研究嗅觉 CYP 功能的有用候选者。