Atg8 is involved in endosomal and phagosomal acidification in the parasitic protist Entamoeba histolytica.

Atg8 is involved in endosomal and phagosomal acidification in the parasitic protist Entamoeba histolytica.
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DOI:
10.1111/cmi.12453
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发表时间:
2015-10
影响因子:
3.4
通讯作者:
Nozaki T
Nozaki T
中科院分区:
生物学2区
文献类型:
--
作者:
Picazarri K;Nakada-Tsukui K;Tsuboi K;Miyamoto E;Watanabe N;Kawakami E;Nozaki T

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自噬是两种主要的蛋白质降解系统之一,在真核生物中是保守的。原生动物溶组织内阿米巴是一种人类肠道寄生虫,与其他真核生物相比,它具有一组有限的自噬相关(Atg)蛋白,因此代表了研究自噬最小必需成分和祖先功能的合适模式生物。溶组织艾美耳球虫有两个接合系统:Atg 8和Atg 5/12,尽管基因组中缺少编码Atg 12的基因。Atg 8被认为是自噬体的中心和真实的标志物,但最近的研究表明,Atg 8不仅参与自噬本身,而且还参与囊泡运输的其他基本机制。为了研究溶组织肠杆菌中的这个问题,我们研究了增殖阶段的Atg 8。Atg 8在实验室维持的和最近建立的临床分离株中组成型表达,并且在对数生长期似乎是脂质修饰的,表明Atg 8在非应激和增殖条件下的作用。这些发现是在相反的侵袭内阿米巴,其中自噬显着诱导分化的早期阶段从滋养体到包囊。通过反义小RNA介导的转录基因沉默抑制溶组织肠杆菌中Atg 8基因表达导致生长迟缓、内吞作用延迟以及内体和吞噬体酸化减少。两者合计,这些结果表明,Atg 8和Atg 8共轭途径在这种原始真核生物的内体和吞噬体的生物发生中具有一定的作用。
Autophagy is one of two major bulk protein degradation systems and is conserved throughout eukaryotes. The protozoan E ntamoeba histolytica, which is a human intestinal parasite, possesses a restricted set of autophagy‐related (Atg) proteins compared with other eukaryotes and thus represents a suitable model organism for studying the minimal essential components and ancestral functions of autophagy. E. histolytica possesses two conjugation systems: Atg8 and Atg5/12, although a gene encoding Atg12 is missing in the genome. Atg8 is considered to be the central and authentic marker of autophagosomes, but recent studies have demonstrated that Atg8 is not exclusively involved in autophagy per se, but other fundamental mechanisms of vesicular traffic. To investigate this question in E . histolytica, we studied on Atg8 during the proliferative stage. Atg8 was constitutively expressed in both laboratory‐maintained and recently established clinical isolates and appeared to be lipid‐modified in logarithmic growth phase, suggesting a role of Atg8 in non‐stress and proliferative conditions. These findings are in contrast to those for E ntamoeba invadens, in which autophagy is markedly induced during an early phase of differentiation from the trophozoite into the cyst. The repression of Atg8 gene expression in En . histolytica by antisense small RNA‐mediated transcriptional gene silencing resulted in growth retardation, delayed endocytosis and reduced acidification of endosomes and phagosomes. Taken together, these results suggest that Atg8 and the Atg8 conjugation pathway have some roles in the biogenesis of endosomes and phagosomes in this primitive eukaryote.