Mosimann Marc, Goshima Shinobu, Wenzler Tanja, Lüscher Alexandra, Uozumi Nobuyuki, Mäser Pascal
Institute of Cell Biology, University of Bern, Bern, Switzerland.
Eukaryot Cell. 2010 Apr;9(4):539-46. doi: 10.1128/EC.00314-09. Epub 2010 Feb 26.
The molecular mechanisms of K(+) homeostasis are only poorly understood for protozoan parasites. Trypanosoma brucei subsp. parasites, the causative agents of human sleeping sickness and nagana, are strictly extracellular and need to actively concentrate K(+) from their hosts' body fluids. The T. brucei genome contains two putative K(+) channel genes, yet the trypanosomes are insensitive to K(+) antagonists and K(+) channel-blocking agents, and they do not spontaneously depolarize in response to high extracellular K(+) concentrations. However, the trypanosomes are extremely sensitive to K(+) ionophores such as valinomycin. Surprisingly, T. brucei possesses a member of the Trk/HKT superfamily of monovalent cation permeases which so far had only been known from bacteria, archaea, fungi, and plants. The protein was named TbHKT1 and functions as a Na(+)-independent K(+) transporter when expressed in Escherichia coli, Saccharomyces cerevisiae, or Xenopus laevis oocytes. In trypanosomes, TbHKT1 is expressed in both the mammalian bloodstream stage and the Tsetse fly midgut stage; however, RNA interference (RNAi)-mediated silencing of TbHKT1 expression did not produce a growth phenotype in either stage. The presence of HKT genes in trypanosomatids adds a further piece to the enigmatic phylogeny of the Trk/HKT superfamily of K(+) transporters. Parsimonial analysis suggests that the transporters were present in the first eukaryotes but subsequently lost in several of the major eukaryotic lineages, in at least four independent events.
对于原生动物寄生虫，钾离子（K⁺）稳态的分子机制目前了解甚少。布氏锥虫亚种寄生虫是人类昏睡病和那加那病的病原体，它们严格生活在细胞外，需要从宿主的体液中主动浓缩K⁺。布氏锥虫基因组包含两个假定的K⁺通道基因，但锥虫对K⁺拮抗剂和K⁺通道阻滞剂不敏感，并且它们不会因细胞外高K⁺浓度而自发去极化。然而，锥虫对缬氨霉素等K⁺离子载体极其敏感。令人惊讶的是，布氏锥虫拥有一个Trk/HKT单价阳离子通透酶超家族的成员，迄今为止，该家族仅在细菌、古细菌、真菌和植物中被发现。该蛋白质被命名为TbHKT1，当在大肠杆菌、酿酒酵母或非洲爪蟾卵母细胞中表达时，它作为一种不依赖Na⁺的K⁺转运体发挥作用。在锥虫中，TbHKT1在哺乳动物血液阶段和采采蝇中肠阶段均有表达；然而，RNA干扰（RNAi）介导的TbHKT1表达沉默在这两个阶段均未产生生长表型。锥虫体内HKT基因的存在为K⁺转运体Trk/HKT超家族神秘的系统发育增添了新的内容。简约分析表明，这些转运体存在于最早的真核生物中，但随后在几个主要的真核生物谱系中至少经历了四次独立事件而丢失。
