研究发现,蚊子通过人体呼出的二氧化碳来寻找食物来源。一旦它们叮咬在人身上,就可以传染很多危险的传染性疾病,如疟疾、黄热病和脑膜炎等。
??近期的《自然》杂志上发表了美国洛克菲勒大学Leslie Vosshall实验室的一项最新研究成果,他们发现了果蝇体内的两种二氧化碳受体分子,是昆虫借以感受二氧化碳的基础。这一发现对于抵御全球性的传染性疾病有重要的意义。
??昆虫对二氧化碳都很敏感,它们利用二氧化碳来寻找食物来源和评估自己的周围环境。研究人员早已经发现了昆虫体内能感受二氧化碳的神经元西细胞,但是神经元如何感受二氧化碳的分子机制一直还不清楚。
??研究发现的Gr21a蛋白,以前被发现在对二氧化碳感应神经元细胞中表达,后者位于果蝇的触角上。因为在苍蝇体内,化学感应受体通常是一些不相关的蛋白一起相互作用。该研究的第一作者Walton Jones因此从研究味觉受体家族开始,他发现Gr63a蛋白同Gr21a蛋白在幼虫和成年果蝇中都是共表达存在的。进一步检测疟疾蚊子发现与果蝇的同源基因GPRGR22和GPRGR24,它们也在蚊子感受二氧化碳的触须上共表达。
??通过分子生物学操作,Jones最终证明Gr63a蛋白同Gr21a蛋白确实是果蝇神经元感受二氧化碳所必须的分子。只有Gr63a同Gr21a一起表达的时候,果蝇才可能感受到二氧化碳,将Gr63a突变后,果蝇对高浓度的二氧化碳都没有表现出正常果蝇的规避行为。
英文原文:
Identification of carbon dioxide receptors in insects may help fight infectious disease
Carbon dioxide-sensitive neurons expressing Gr21a (green) and Gr63a (red), proteins that together (white) are necessary for carbon dioxide detection. The neurons target a specific region of the fly brain, which is dedicated to processing the smell of carbon dioxide.
Mosquitoes don’t mind morning breath. They use the carbon dioxide people exhale as a way to identify a potential food source. But when they bite, they can pass on a number of dangerous infectious diseases, such as malaria, yellow fever, and West Nile encephalitis. Now, reporting in today’s advance online publication in Nature, Leslie Vosshall’s laboratory at Rockefeller University has identified the two molecular receptors in fruit flies that help these insects detect carbon dioxide. The findings could prove to be important against the fight against global infectious disease.
"Insects are especially sensitive to carbon dioxide, using it to track food sources and assess their surrounding environment," says Vosshall, Chemers Family Associate Professor and head of the Laboratory of Neurogenetics and Behavior at Rockefeller. "The neurons in insects that respond to carbon dioxide were already known, but the molecular mechanism by which these neurons sense this gas was a mystery."
One protein, called Gr21a, was previously known to be expressed in the carbon dioxide responsive neurons, which are in the antennae of the fruit fly. Since in the fly, chemosensory receptors usually work together as a pair of unrelated proteins, Walton Jones, a former biomedical fellow and first author of the paper, began by looking for other members of the gustatory receptor family, and found that the Gr63a protein was always co-expressed with Gr21a, both in the larva and in the adult fly.
"I went on to look at the malaria mosquito and found two homologues of the fly genes, GPRGR22 and GPRGR24. They are also co-expressed in the mosquito’s maxillary palp, the appendage mosquitoes use to sense carbon dioxide," says Jones.
Using genetic manipulation, Jones was able to show that both Gr21a and Gr63a are all that is needed for a fly neuron to sense carbon dioxide. He took neurons that did not normally respond to carbon dioxide and found that only if he expressed both Gr21a and Gr63a together, those neurons now became excited by the gas. He also showed that when Gr63a is mutated, the mutant flies no longer respond to the high levels of carbon dioxide that wild type flies avoid.
These molecules are the first membrane-associated proteins that have been shown to sense a gas. All previously described gas sensors have been cytoplasmic. "Though we don’t know what other proteins might be involved in the signaling pathway, the identification of the carbon dioxide receptor provides a potential target for the design of inhibitors that would act as an insect repellent, "says Vosshall. "These inhibitors would help fight global infectious disease by reducing the attraction of blood-feeding insects to humans."