《柳葉刀》雜志在1989年曾經(jīng)刊載了一則有趣的報(bào)告，一條狗總是愛舔主人腿上的一顆痣——這顆痣最終演變成一個(gè)惡性黑素瘤,。從那時(shí)開始,，科學(xué)家相繼在大鼠和小鼠中觀察到類似的“嗅出疾病”的能力，這種能力幫助這些嚙齒動(dòng)物遠(yuǎn)離種群中生病的成員,。如今,，研究人員相信他們已經(jīng)搞清了這些動(dòng)物是如何具有這項(xiàng)本領(lǐng)的。
科學(xué)家之前已經(jīng)鑒別出了許多小鼠嗅覺受體——動(dòng)物鼻腔中的細(xì)胞表面蛋白質(zhì),，能夠感知從食物的香味到恐懼的氣味的每一種事物,。瑞士日內(nèi)瓦大學(xué)的神經(jīng)遺傳學(xué)家Ivan Rodriguez和同事尋思，這里是否還有一種額外的受體,，能夠?qū)膊〉?ldquo;氣味”作出響應(yīng)——多半是通過探測與細(xì)菌和炎癥相關(guān)的化學(xué)物質(zhì)來實(shí)現(xiàn),。
研究人員搜索了已經(jīng)破譯的小鼠基因組，在它的嗅覺系統(tǒng)中尋找可能編碼額外受體蛋白質(zhì)的基因,，以及連接鼻腔和大腦的感覺細(xì)胞。研究人員發(fā)現(xiàn)了5個(gè)新受體的基因,，所有的基因都屬于一類已知的蛋白質(zhì)——甲酰肽受體(FPRs),。
FPRs包含有兩類免疫系統(tǒng)受體，能夠探測從血液中的病原體內(nèi)散發(fā)的化學(xué)物質(zhì),，從而幫助免疫細(xì)胞追捕到并且攻擊外來物體,。那么在嗅覺細(xì)胞上新鑒別出的受體是否具有類似的功能呢——即能夠探測其他動(dòng)物體內(nèi)的病原體？在實(shí)驗(yàn)室中,，Rodriguez的研究小組將小鼠的嗅覺神經(jīng)細(xì)胞暴露在能夠?qū)е录膊〉募?xì)菌以及患病小鼠的尿液中,。毫無疑問，某些化學(xué)物質(zhì)“點(diǎn)燃”了神經(jīng)細(xì)胞中的一種“嗅覺響應(yīng)”,，其表現(xiàn)為細(xì)胞電位變化,。研究人員日前在《自然》雜志網(wǎng)絡(luò)版上報(bào)告了這一研究成果。
這些神經(jīng)細(xì)胞所擁有的新發(fā)現(xiàn)的FPR受體位于大腦基部的嗅覺系統(tǒng)中,，這里同時(shí)還能夠嗅出名為信息素的性信號化學(xué)物質(zhì),。這一區(qū)域——犁鼻器——直接連接到大腦的情緒中心——扁桃體,。Rodriguez認(rèn)為：“這具有重要的意義。”他說,，當(dāng)一只小鼠探測到附近的伴侶,，或危險(xiǎn)——某種形式的疾病，它需要觸發(fā)一種快速響應(yīng),，例如嘗試繁殖,，或遠(yuǎn)離附近患病的動(dòng)物。
Rodriguez的研究小組同時(shí)在沙鼠和大鼠中也發(fā)現(xiàn)了疾病嗅覺受體,，但是他認(rèn)為不太可能在人類的鼻腔中發(fā)現(xiàn)這種受體,。他說，除了免疫系統(tǒng)外,，沒有證據(jù)表明在人體的其他組織中存在FPRs,。
法國巴黎市巴斯德研究所的神經(jīng)科學(xué)家及嗅覺專家Pierre Marie Lledo認(rèn)為，這些研究成果“非常令人興奮,，很有可能是一項(xiàng)大的突破”,。瑞士洛桑大學(xué)的嗅覺研究專家Marie-Christine Broillet指出，這一發(fā)現(xiàn)為搞清用嗅覺發(fā)現(xiàn)疾病的分子機(jī)制開辟了“一個(gè)新的研究領(lǐng)域”,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature advance online publication 22 April 2009 | doi:10.1038/nature08029
Formyl peptide receptor-like proteins are a novel family of vomeronasal chemosensors
Stéphane Rivière1,3, Ludivine Challet1,3, Daniela Fluegge2,3,4, Marc Spehr2,4 & Ivan Rodriguez1
1 Department of Zoology and Animal Biology, and National Center of Competence 'Frontiers in Genetics', University of Geneva, 1205 Geneva, Switzerland
2 Department of Cellular Physiology, Ruhr University, 44780 Bochum, Germany
3 These authors contributed equally to this work.
4 Present address: Department of Chemosensation, Institute of Biology II, RWTH Aachen University, 52074 Aachen, Germany.
Correspondence to: Ivan Rodriguez1 Correspondence and requests for materials should be addressed to I.R.
Mammals rely heavily on olfaction to interact adequately with each other and with their environment1. They make use of seven-transmembrane G-protein-coupled receptors to identify odorants and pheromones. These receptors are present on dendrites of olfactory sensory neurons located in the main olfactory or vomeronasal sensory epithelia, and pertain to the odorant2, trace amine-associated receptor3 and vomeronasal type 1 (ref. 4) or 2 (refs 5–7) receptor superfamilies. Whether these four sensor classes represent the complete olfactory molecular repertoire used by mammals to make sense of the outside world is unknown. Here we report the expression of formyl peptide receptor-related genes by vomeronasal sensory neurons, in multiple mammalian species. Similar to the four known olfactory receptor gene classes, these genes encode seven-transmembrane proteins, and are characterized by monogenic transcription and a punctate expression pattern in the sensory neuroepithelium. In vitro expression of mouse formyl peptide receptor-like 1, 3, 4, 6 and 7 provides sensitivity to disease/inflammation-related ligands. Establishing an in situ approach that combines whole-mount vomeronasal preparations with dendritic calcium imaging in the intact neuroepithelium, we show neuronal responses to the same molecules, which therefore represent a new class of vomeronasal agonists. Taken together, these results suggest that formyl peptide receptor-like proteins have an olfactory function associated with the identification of pathogens, or of pathogenic states.
