Rinker David C, Jones Patrick L, Pitts R Jason, Rutzler Michael, Camp Gray, Sun Lujuan, Xu Pingxi, Weaver David, Zwiebel Laurence J
Center for Human Genetics Training Program, Vanderbilt University Medical Centre, Nashville, U.S.A.
Department of Biological Sciences, Vanderbilt University, Nashville, U.S.A.
Physiol Entomol. 2012 Mar;37(1):33-41. doi: 10.1111/j.1365-3032.2011.00821.x. Epub 2012 Feb 23.
Despite many decades of multilateral global efforts, a significant portion of the world population continues to be plagued with one or more mosquito-vectored diseases. These include malaria and filariasis as well as numerous arboviral-associated illnesses including Dengue and Yellow fevers. The dynamics of disease transmission by mosquitoes is complex, and involves both vector competence and vectorial capacity. One area of intensive effort is the study of chemosensory-driven behaviours in the malaria vector mosquito Giles, the modulation of which are likely to provide opportunities for disease reduction. In this context recent studies have characterized a large divergent family of odorant receptors (AgORs) that play critical roles in olfactory signal transduction. This work has facilitated high-throughput, cell-based calcium mobilization screens of AgOR-expressing HEK cells that have identified a large number of conventional AgOR ligands, as well as the first non-conventional Orco (olfactory receptor co-receptor) family agonist. As such, ligand-mediated modulation serves as a proof-of-concept demonstration that AgORs represent viable targets for high-throughput screening and for the eventual development of behaviour-modifying olfactory compounds. Such attractants or repellents could foster malaria reduction programmes.
尽管全球进行了数十年的多边努力，但世界上仍有很大一部分人口继续受到一种或多种蚊媒疾病的困扰。这些疾病包括疟疾和丝虫病，以及许多与虫媒病毒相关的疾病，如登革热和黄热病。蚊子传播疾病的动态过程很复杂，涉及媒介能力和传病力。一个重点研究领域是对疟蚊吉氏按蚊中化学感应驱动行为的研究，对其进行调控可能为减少疾病提供机会。在此背景下，最近的研究对一大类不同的气味受体（AgORs）进行了表征，这些受体在嗅觉信号转导中起关键作用。这项工作推动了基于细胞的高通量钙动员筛选，该筛选针对表达AgOR的HEK细胞，已鉴定出大量传统的AgOR配体，以及首个非常规的嗅觉受体共受体（Orco）家族激动剂。因此，配体介导的调控作为一种概念验证，证明AgORs是高通量筛选以及最终开发改变行为的嗅觉化合物的可行靶点。此类引诱剂或驱避剂可促进疟疾防治计划。
