Remodeling the Specificity of an Endosomal CORVET Tether Underlies Formation of Regulated Secretory Vesicles in the Ciliate Tetrahymena thermophila.
Remodeling the Specificity of an Endosomal CORVET Tether Underlies Formation of Regulated Secretory Vesicles in the Ciliate Tetrahymena thermophila.
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DOI：
10.1016/j.cub.2018.01.047
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发表时间：
2018-03-05
期刊：
影响因子：
--
通讯作者：
Turkewitz AP
中科院分区：
文献类型：
--
作者：
Sparvoli D;Richardson E;Osakada H;Lan X;Iwamoto M;Bowman GR;Kontur C;Bourland WA;Lynn DH;Pritchard JK;Haraguchi T;Dacks JB;Turkewitz AP
在动物的内吞途径中，两个相关的复合体，称为CORVET(C类核心空泡/内小体运输)和HOPPS(同型融合和蛋白质分类)，分别作为早期和晚期内小体的纽带和融合因子。CORVET或啤酒花的突变会导致运输缺陷，并导致包括免疫功能障碍在内的人类疾病。Hop和CORVET在真核生物中都是保守的，但值得注意的是，在纤毛虫四膜虫中，Hop特异的亚基缺失，而CORVET特异的亚基增殖。VPS8(液泡蛋白分类)是一个CORVET亚基，在四膜虫中扩增到6个平行对数。这种扩张与纤毛虫亚群中啤酒花的损失有关，其中包括含有四膜虫的寡膜壳虫。通过正向遗传学发现，四膜虫中的单个VPS8准同源基因(VPS8A)需要合成称为粘液囊的显著分泌颗粒。更具体地说，Δvps8a细胞不能向发育中的粘液囊递送货物蛋白的子集，而是将货物积累在也带有粘液囊分类受体Sor4p的囊泡中。令人惊讶的是，尽管这一转运步骤依赖于CORVET，但它似乎并不涉及早期的内小体。相反，Vps8a与晚期内体/溶酶体标记Rab7相关联，表明在纤毛虫的进化过程中，CORVET亚基发生了靶标特异性转换。粘液囊属于一类种类繁多且研究较少的原生分泌细胞器，称为Extrusome。我们的结果强调粘液囊的生物发生依赖于内溶酶体的运输，揭示了与顶复合体寄生虫中侵袭细胞器的相似之处，并表明原生动物，如动物，广泛的分泌适应依赖于与溶酶体生物发生相关的机制。Sparvoli等人报道了真核膜运输中的一个值得注意的场景，其中保守决定簇的特定线性损失通过相关复合体中的扩展和特异性变化来平衡。这阐明了与溶酶体形成有关的机制在真核生物中产生精细的分泌囊泡的重要性。
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, Δvps8a 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/lysosomal marker Rab7, indicating 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. Sparvoli et al report a remarkable scenario in eukaryotic membrane trafficking, where lineagespecific loss of a conserved determinant was balanced by expansion and change-of-specificity in a related complex. This sheds light on the importance of mechanisms associated with lysosome formation in generating elaborate secretory vesicles in eukaryotes.
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影响因子：
3.3
作者：
Cowan, AT;Bowman, GR;Turkewitz, AP
通讯作者：
Turkewitz, AP
DOI：
10.1038/85012
发表时间：
2001-03-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Dulubova, I;Yamaguchi, T;Rizo, J
通讯作者：
Rizo, J
影响因子：
4
作者：
Balderhaar, Henning J. Kleine;Ungermann, Christian
通讯作者：
Ungermann, Christian
影响因子：
4
作者：
Elias, Marek;Brighouse, Andrew;Dacks, Joel B.
通讯作者：
Dacks, Joel B.
颗粒晶格蛋白1（Grl1p）是嗜热四膜虫密核分泌颗粒中的一种酸性钙结合蛋白，它影响颗粒的大小、形状、内容物组织和释放，但不影响蛋白质的分选或凝聚
影响因子：
7.8
作者：
Chilcoat, ND;Melia, SM;Turkewitz, AP
通讯作者：
Turkewitz, AP