Engstler Markus, Boshart Michael
Ludwig-Maximilians-Universität, Department Biologie I, Genetik, 80638 München, Germany.
Genes Dev. 2004 Nov 15;18(22):2798-811. doi: 10.1101/gad.323404.
Transmission of a protozoan parasite from a vertebrate to invertebrate host is accompanied by cellular differentiation. The signals from the environment that trigger the process are poorly understood. The model parasite Trypanosoma brucei proliferates in the mammalian bloodstream and in the tsetse fly. On ingestion by the tsetse, the trypanosome undergoes a rapid differentiation that is marked by replacement of the variant surface glycoprotein (VSG) coat with GPI-anchored EP and GPEET procyclins. Here we show that a cold shock of DeltaT > 15 degrees C is sufficient to reversibly induce high-level expression of the insect stage-specific EP gene in the mammalian bloodstream stages of T. brucei. The 3'-UTR of the EP mRNA is necessary and sufficient for the increased expression. During cold shock, EP protein accumulates in the endosomal compartment in the proliferating, slender, bloodstream stage, whereas the EP is present on the plasma membrane in the quiescent, stumpy, bloodstream stage. Thus, there is a novel developmentally regulated cell surface access control mechanism for a GPI-anchored protein. In addition to inducing EP expression, cold shock results in the acquisition of sensitivity to micromolar concentrations of cis-aconitate and citrate by stumpy but not slender bloodstream forms. The cis-aconitate and citrate commit stumpy bloodstream cells to differentiation to the procyclic stage along with rapid initial proliferation. We propose a hierarchical model of three events that regulate differentiation after transmission to the tsetse: sensing the temperature change, surface access of a putative receptor, and sensing of a chemical cue.
原生动物寄生虫从脊椎动物宿主传播到无脊椎动物宿主的过程伴随着细胞分化。触发这一过程的环境信号目前还知之甚少。模式寄生虫布氏锥虫在哺乳动物血液和采采蝇中增殖。被采采蝇摄入后，锥虫会经历快速分化，其特征是用糖基磷脂酰肌醇（GPI）锚定的EP和GPEET前环素取代可变表面糖蛋白（VSG）外衣。在此，我们表明，ΔT > 15摄氏度的冷休克足以在布氏锥虫的哺乳动物血液阶段可逆地诱导昆虫阶段特异性EP基因的高水平表达。EP mRNA的3'-非翻译区对于表达增加是必要且充分的。在冷休克期间，EP蛋白在增殖的、细长的血液阶段的内体区室中积累，而在静止的、粗短的血液阶段，EP存在于质膜上。因此，对于一种GPI锚定蛋白存在一种新的发育调控的细胞表面可及性控制机制。除了诱导EP表达外，冷休克还导致粗短而非细长的血液形式对微摩尔浓度的顺乌头酸和柠檬酸盐产生敏感性。顺乌头酸和柠檬酸盐使粗短的血液细胞开始分化为前循环阶段，并伴有快速的初始增殖。我们提出了一个三级模型，用于解释传播到采采蝇后调节分化的三个事件：感知温度变化、假定受体的表面可及性以及感知化学信号。
