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首页> 外文期刊>Current Biology: CB >Remodeling the Specificity of an Endosomal CORVET Tether Underlies Formation of Regulated Secretory Vesicles in the Ciliate Tetrahymena thermophila
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Remodeling the Specificity of an Endosomal CORVET Tether Underlies Formation of Regulated Secretory Vesicles in the Ciliate Tetrahymena thermophila

机译：重塑内体慢率系绳的特异性在CiLiate Tetrahymena Heathophila中形成受调节的分泌囊泡的形成

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In the endocytic pathway of animals, two related complexes, called CORVET (class C core vacuole/endosome transport) and HOPS (homotypic fusion and protein sorting), act as both tethers and fusion factors for early and late endosomes, respectively. Mutations in CORVET or HOPS lead to trafficking defects and contribute to human disease, including immune dysfunction. HOPS and CORVET are conserved throughout eukaryotes, but remarkably, in the ciliate Tetrahymena thermophila, the HOPS-specific subunits are absent, while CORVET-specific subunits have proliferated. VPS8 (vacuolar protein sorting), a CORVET subunit, expanded to 6 paralogs in Tetrahymena. This expansion correlated with loss of HOPS within a ciliate subgroup, including the Oligohymenophorea, which contains Tetrahymena. As uncovered via forward genetics, a single VPS8 paralog in Tetrahymena (VPS8A) is required to synthesize prominent secretory granules called mucocysts. More specifically, Dvps8a cells fail to deliver a subset of cargo proteins to developing mucocysts, instead accumulating that cargo in vesicles also bearing the mucocyst-sorting receptor Sor4p. Surprisingly, although this transport step relies on CORVET, it does not appear to involve early endosomes. Instead, Vps8a associates with the late endosomal/lyso somal marker Rab7, indicating that target specificity switching occurred in CORVET subunits during the evolution of ciliates. Mucocysts belong to a markedly diverse and understudied class of protist secretory organelles called extrusomes. Our results underscore that biogenesis of mucocysts depends on endolysosomal trafficking, revealing parallels with invasive organelles in apicomplexan parasites and suggesting that a wide array of secretory adaptations in protists, like in animals, depend on mechanisms related to lysosome biogenesis.
机译：在动物的内吞径中，两个相关的络合物，称为慢性（C芯芳芯/内体输送）和跳跃（均型融合和蛋白质分选），分别作为早期和晚期的重生和融合因子。 Corvet或HOPS中的突变导致贩运缺陷并有助于人类疾病，包括免疫功能障碍。啤酒花和慢速在整个真核生物中保存，但显着地，在CileiateTavymena Heathophila中，啤酒花特异性亚基是不存在的，而猪特异性亚基具有增殖。 VPS8（真空蛋白质分选），肉豆蔻亚基，在四腹膜中扩增至6个旁系蛋白酶。这种膨胀与含有寡核聚心的含量亚组中的啤酒花中的丧失相关，其中含有四氢脲。由于通过前向遗传学揭示，需要在四瘤塞（VPS8A）中的单个VPS8副病毒，以合成称为粘膜的突出分泌颗粒。更具体地，DVPS8A细胞未能将货物蛋白质的子集递送至显影粘膜，而是在囊泡中的囊泡中累积成粘膜中的货物也累积。令人惊讶的是，虽然这种运输步骤依赖于慢慢，但它似乎没有涉及早期的内体。相反，VPS8A与晚期内体/ LysoMomal标记Rab7相关联，表明在Ciliates演变过程中的Corvet亚基中发生了目标特异性切换。粘膜属于一种明显多样化，也是众所周为人的蛋白质分泌细胞器，称为外泌体。我们的结果强调了粘膜生物囊体的生物发生依赖于内炎血吸虫贩运，在Apicomplexan寄生虫中揭示了具有侵袭性细胞器的平扰，并表明在动物中，如动物的各种分泌物适应依赖于与溶酶体生物发生相关的机制。

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