A Receptor's Tale: An Eon in the Life of a Trypanosome Receptor.
A Receptor's Tale: An Eon in the Life of a Trypanosome Receptor.
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一个受体的故事：锥虫受体生命中的eon。
DOI：
10.1371/journal.ppat.1006055
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发表时间：
2017-01
期刊：
影响因子：
6.7
通讯作者：
Carrington M
中科院分区：
文献类型：
--
作者：
Higgins MK;Lane-Serff H;MacGregor P;Carrington M
非洲锥虫具有复杂的生活史，包括至少十种发育形式，以不同的方式适应采采蝇媒介和哺乳动物宿主的不同生态位。与许多其他原生动物病原体不同，它们总是在细胞外，并进化出复杂的表面涂层，使它们能够获得营养，同时保护它们免受昆虫或哺乳动物的免疫防御。大分子营养素的获取需要在这些表面涂层的背景下发挥作用的受体。其中最了解的是布鲁氏锥虫的结合珠蛋白-血红蛋白受体(HpHbR)，这种寄生虫的哺乳动物血液形式利用它来获得血红素。然而，在一些灵长类动物中，它也提供了一条摄取锥虫溶解因子-1的途径，该因子是对抗锥虫感染的先天免疫的媒介。最近的研究表明，在非洲锥虫物种的进化过程中，受体的功能发生了变化，从主要在采采蝇中表达的血红蛋白受体到主要在哺乳动物血液中表达的结合珠蛋白-血红蛋白受体。对不同锥体物种同源受体的结构和功能的研究使我们能够提出一种受体如何适应不同锥体物种中不同角色的进化史。他们还强调了受体在复杂的锥虫表面上工作所面临的挑战，并展示了如何应对这些挑战。
African trypanosomes have complex life cycles comprising at least ten developmental forms, variously adapted to different niches in their tsetse fly vector and their mammalian hosts. Unlike many other protozoan pathogens, they are always extracellular and have evolved intricate surface coats that allow them to obtain nutrients while also protecting them from the immune defenses of either insects or mammals. The acquisition of macromolecular nutrients requires receptors that function within the context of these surface coats. The best understood of these is the haptoglobin–hemoglobin receptor (HpHbR) of Trypanosoma brucei, which is used by the mammalian bloodstream form of the parasite, allowing heme acquisition. However, in some primates it also provides an uptake route for trypanolytic factor-1, a mediator of innate immunity against trypanosome infection. Recent studies have shown that during the evolution of African trypanosome species the receptor has diversified in function from a hemoglobin receptor predominantly expressed in the tsetse fly to a haptoglobin–hemoglobin receptor predominantly expressed in the mammalian bloodstream. Structural and functional studies of homologous receptors from different trypanosome species have allowed us to propose an evolutionary history for how one receptor has adapted to different roles in different trypanosome species. They also highlight the challenges that a receptor faces in operating on the complex trypanosome surface and show how these challenges can be met.