Chen Stephanie Turner, Kowalewski Joel, Ray Anandasankar
Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA 92521, USA.
Interdepartmental Neuroscience Program, University of California, Riverside, CA 92521, USA.
Interface Focus. 2021 Apr 6;11(2):20200043. doi: 10.1098/rsfs.2020.0043. Epub 2021 Feb 12.
Many insects can detect carbon dioxide (CO) plumes using a conserved receptor made up of members of the gustatory receptor (Gr) family Gr1, Gr2 and Gr3. Mosquitoes are attracted to host animals for blood meals using plumes of CO in the exhaled breath using the receptor expressed in the A neuron of the capitate peg sensilla type on the maxillary palps. The receptor is known to also detect several other classes of odorants, including ones emitted from human skin. Here, we discover that a common skin odorant, butyric acid, can cause a phasic activation followed by an unusually prolonged tonic activity after the stimulus is over in the CO neurons of mosquitoes. The effect is conserved in both and mosquitoes. This raises a question about its role in a mosquito's preference for the skin odour of different individuals. Butyric acid belongs to a small number of odorants known to cause the prolonged activation of the CO receptor. A chemical informatic analysis identifies a specific set of physico-chemical features that can be used in a machine learning predictive model for the prolonged activators. Interestingly, this set is different from physico-chemical features selected for activators or inhibitors, indicating that each has a distinct structural basis. The structural understanding opens up an opportunity to find novel ligands to manipulate the CO receptor and mosquito behaviour.
许多昆虫能够利用一种由味觉受体(Gr)家族的Gr1、Gr2和Gr3成员组成的保守受体来检测二氧化碳(CO)羽流。蚊子利用上颌触须上头状钉形感器A神经元中表达的受体,通过呼出气体中的CO羽流被宿主动物吸引来获取血液。已知该受体还能检测其他几类气味分子,包括从人类皮肤散发的气味分子。在这里,我们发现一种常见的皮肤气味分子丁酸,在刺激结束后,会在蚊子的CO神经元中引起阶段性激活,随后是异常延长的紧张性活动。这种效应在[具体种类1]和[具体种类2]蚊子中都存在。这就引发了一个问题,即它在蚊子对不同个体皮肤气味的偏好中所起的作用。丁酸属于已知能导致CO受体长时间激活的少数气味分子之一。化学信息学分析确定了一组特定的物理化学特征,可用于构建关于长时间激活剂的机器学习预测模型。有趣的是,这组特征与为激活剂或抑制剂选择的物理化学特征不同,表明它们各自具有独特的结构基础。这种结构上的理解为寻找新型配体以操纵CO受体和蚊子行为提供了机会。