Blocking variant surface glycoprotein synthesis alters endoplasmic reticulum exit sites/Golgi homeostasis in Trypanosoma brucei.
Blocking variant surface glycoprotein synthesis alters endoplasmic reticulum exit sites/Golgi homeostasis in Trypanosoma brucei.
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DOI：
10.1111/tra.12561
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Rudenko G
中科院分区：
文献类型：
--
作者：
Ooi CP;Smith TK;Gluenz E;Wand NV;Vaughan S;Rudenko G
布氏锥虫血液的主要分泌物是变异型表面糖蛋白(VSG)，约占总蛋白的10%，并形成致密的保护层。使用Morpholino寡核苷酸阻断VSG的翻译会触发精确的胞质分裂前停滞。我们研究了阻断VSG合成对分泌途径的影响。高尔基体数量减少，尤其是有丝分裂后细胞，从3.5±0.6个/细胞减少到2.0±0.04个/细胞。同样，有丝分裂后细胞内质网出口部位(ERE)的数量在阻断VSG合成8小时后从3.9±0.6降至2.7±0.1 。在这些停滞的细胞中，分泌途径仍然起作用，正如组织蛋白酶L所监测的那样，磷脂和糖基磷脂酰肌醇锚定生物合成的速率相对保持不受影响，除了鞘磷脂的水平增加。然而，内质网和高尔基体形态都变得扭曲，高尔基体池明显扩张，尤其是在横面。这些结构中的膜堆积可能是由于分泌货物总量急剧减少，即VSG，导致新生小泡萌发减少所致。这些数据表明，分泌物的总通量影响布氏毛虫分泌结构和细胞器的生物发生和维持，包括ERES和高尔基体。
The predominant secretory cargo of bloodstream form Trypanosoma brucei is variant surface glycoprotein (VSG), comprising ~10% total protein and forming a dense protective layer. Blocking VSG translation using Morpholino oligonucleotides triggered a precise pre‐cytokinesis arrest. We investigated the effect of blocking VSG synthesis on the secretory pathway. The number of Golgi decreased, particularly in post‐mitotic cells, from 3.5 ± 0.6 to 2.0 ± 0.04 per cell. Similarly, the number of endoplasmic reticulum exit sites (ERES) in post‐mitotic cells dropped from 3.9 ± 0.6 to 2.7 ± 0.1 eight hours after blocking VSG synthesis. The secretory pathway was still functional in these stalled cells, as monitored using Cathepsin L. Rates of phospholipid and glycosylphosphatidylinositol‐anchor biosynthesis remained relatively unaffected, except for the level of sphingomyelin which increased. However, both endoplasmic reticulum and Golgi morphology became distorted, with the Golgi cisternae becoming significantly dilated, particularly at the trans‐face. Membrane accumulation in these structures is possibly caused by reduced budding of nascent vesicles due to the drastic reduction in the total amount of secretory cargo, that is, VSG. These data argue that the total flux of secretory cargo impacts upon the biogenesis and maintenance of secretory structures and organelles in T. brucei, including the ERES and Golgi.
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