Trypanosoma brucei:: TbRAB4 regulates membrane recycling and expression of surface proteins in procyclic forms
Trypanosoma brucei:: TbRAB4 regulates membrane recycling and expression of surface proteins in procyclic forms
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DOI：
10.1016/j.exppara.2005.07.005
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发表时间：
2005-11-01
影响因子：
2.1
通讯作者：
Field, MC
中科院分区：
文献类型：
--
作者：
Hall, BS;Pal, A;Field, MC
TbRAB 4是布氏锥虫（Trypanosoma brucei）的小GTbRAB 4的直向同源物，其涉及早期内吞作用和再循环过程的控制。TbRAB 4在前循环和血流阶段组成性表达，表明在整个锥虫生命周期中具有重要功能。我们实验室以前的工作表明TbRAB 4在血流形式中是必不可少的。双链TbRAB 4 RNA表达的诱导导致TbRAB 4蛋白水平的特异性降低和对前环形式布氏锥虫生长的抑制，如用荧光团FM 4 -64测量的，摄取和再循环发生改变。过表达GTP锁定的TbRAB 4（QL）突变体的锥虫表现出显着的内吞和再循环途径的扰动，以及破坏GPI锚定蛋白的表面表达。最重要的是，无论是内源性GPI锚定的原环素和异位表达的GPI锚定蛋白，变异的表面糖蛋白，从表面重新定位到TbRAB 4突变细胞的内部网站。这些数据表明，TbRAB 4是重要的脂质锚定蛋白的正常表面表达的维持，并牵连循环途径作为因子的调节表面蛋白的表达在前环锥虫。Rab 4在真核生物进化过程中的功能保守性表明Rab 4介导的运输途径是内吞系统中一个非常古老的组成部分。(c)2005年爱思唯尔公司All rights reserved.
TbRAB4 is the Trypanosoma brucei orthologue of the small GTPase Rab4, which is implicated in the control of early endocytosis and recycling processes. TbRAB4 is expressed constitutively in the procyclic and bloodstream stages suggesting an important function throughout the trypanosome life-cycle. Previous work from our laboratory has shown TbRAB4 to be essential in the bloodstream form. Induction of double-stranded TbRAB4 RNA expression leads to a specific reduction in TbRAB4 protein levels and inhibition of growth in procyclic form T brucei, with alterations in uptake and recycling as measured with the fluorophore FM4-64. Trypanosomes overexpressing GTP-locked TbRAB4(QL) mutants exhibit significant perturbations of endocytic and recycling pathways as well as disruption of surface expression of GPI-anchored proteins. Most significantly, both the endogenous GPI-anchored procyclins and an ectopically expressed GPI-anchored protein, the variant surface glycoprotein, are relocated from the surface to internal sites in TbRAB4 mutant cells. These data indicate that TbRAB4 is important in maintenance of normal surface expression of lipid-anchored proteins, and implicate recycling pathways as factors for modulation of surface protein expression in the procyclic trypanosome. The conservation of function of Rab4 throughout eukaryotic evolution demonstrated here indicates that the Rab4-mediated trafficking pathway is an extremely ancient component of the endocytic system. (c) 2005 Elsevier Inc. All rights reserved.