Two StAR-related lipid transfer proteins play specific roles in endocytosis, exocytosis, and motility in the parasitic protist Entamoeba histolytica.

Two StAR-related lipid transfer proteins play specific roles in endocytosis, exocytosis, and motility in the parasitic protist Entamoeba histolytica.
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DOI:
10.1371/journal.ppat.1009551
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发表时间:
2021-04
期刊:
影响因子:
6.7
通讯作者:
Nozaki T
Nozaki T
中科院分区:
医学1区
文献类型:
--
作者:
Das K;Watanabe N;Nozaki T

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脂质转移蛋白(LTP)是细胞器特异性脂质分布和细胞脂质稳态的关键贡献者。在这里,我们报告了一个新的暗示LTP的吞噬,胞吞,胞饮,生物合成分泌,胞饮体的回收,和运动的寄生原生生物E。溶组织阿米巴,人类阿米巴病的病原体。我们发现,两个与StAR相关的脂质转移(START)结构域包含LTP(命名为EhLTP1和3)参与这些生物学途径中的LTP特异性的方式。我们的研究结果提供了新的影响LTP,这是相关的寄生原生生物引起的疾病的病理生理学的阐明。我们发现EhLTP 1(而不是EhLTP 3)参与半胱氨酸蛋白酶(宿主细胞和细胞外基质的公认降解因子)的分泌,以及伪足的形成和迁移。相反,EhLTP3,而不是EhLTP1,是专门参与胞饮的液相标记。EhLTP1和EhLTP3也参与活哺乳动物细胞的胞吞作用(通过啃食摄取)和死细胞的吞噬作用。在胞啃作用和吞噬作用中,这两种LTP显示出不同的募集模式:例如,EhLTP1在胞吞作用开始时与配体附着位点相关,随后在胞吞作用的中间阶段在胞吞体关闭之前将EhLTP3募集到“胞吞通道”上。这种时空协调的参与过程中的trogo和吞噬作用的LTP从未被证明在单细胞真核生物。LTP也没有被证明参与内吞和胞吐。
Lipid transfer proteins (LTPs) are the key contributor of organelle-specific lipid distribution and cellular lipid homeostasis. Here, we report a novel implication of LTPs in phagocytosis, trogocytosis, pinocytosis, biosynthetic secretion, recycling of pinosomes, and motility of the parasitic protist E. histolytica, the etiological agent of human amoebiasis. We show that two StAR-related lipid transfer (START) domain-containing LTPs (named as EhLTP1 and 3) are involved in these biological pathways in an LTP-specific manner. Our findings provide novel implications of LTPs, which are relevant to the elucidation of pathophysiology of the diseases caused by parasitic protists. We showed that EhLTP1, but not EhLTP3, is involved in secretion of cysteine protease, the well-established degrading factor of host cells and the extracellular matrix, and in pseudopod formation and migration. In contrast, EhLTP3, but not EhLTP1, is exclusively involved in pinocytosis of the fluid-phase marker. Both EhLTP1 and EhLTP3 are also involved in trogocytosis (ingestion by nibbling) of live mammalian cells and phagocytosis of dead cells. In trogocytosis and phagcytosis, these two LTPs displayed distinct patterns of recruitment: e.g., EhLTP1 was associated at the ligand attachment site at the initiation of trogocytosis, followed by the recruitment of EhLTP3 onto the “trogocytic tunnel” at the intermediate stage of trogocytosis before the closure of the trogosome. Such tempo-spatially coordinated involvement of LTPs in the course of trogo- and phagocytosis has never been demonstrated in unicellular eukaryotes. Neither has LTP been shown to be involved in both endocytosis and exocytosis.
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