Tiered assembly of the yeast Far3-7-8-9-10-11 complex at the endoplasmic reticulum.
Tiered assembly of the yeast Far3-7-8-9-10-11 complex at the endoplasmic reticulum.
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酵母 Far3-7-8-9-10-11 复合物在内质网的分层组装。
DOI：
10.1074/jbc.m113.451674
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Liu,Zhengchang
中科院分区：
文献类型：
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作者：
Pracheil,Tammy;Liu,Zhengchang
雷帕霉素信号转导的靶点是一个保守的、整合营养信号与细胞生长和增殖的重要途径。雷帕霉素激酶的靶标存在于两种不同的复合物中，TORC 1和TORC 2。据报道，蛋白磷酸酶2A（PP 2A）和Far 3 -7-8-9-10-11复合物（Far复合物）负调控酵母中的TORC 2信号传导。Far复合物最初被鉴定为信息素诱导的细胞周期停滞所需的因子，PP 2A形成了STRIPAK复合物的酵母对应物，该复合物首先在哺乳动物中分离。Far复合体的细胞定位尚未得到充分表征。在这里，我们表明，Far复合物定位于内质网（ER）通过分析功能的GFP标记的Far蛋白在体内。我们发现，Far 9和Far 10，两个同源的蛋白质，每个具有一个尾部锚定结构域，定位于ER的突变细胞缺乏其他远复杂的组件。Far 3、Far 7和Far 8形成一个亚复合物，由Far 9/10募集到ER。Far 3 -7-8-复合体反过来将Far 11招募到ER。最后，我们证明了Far 9的尾锚结构域是其在TORC 2信号传导中的最佳功能所必需的。我们的研究揭示了酵母Far复合物在ER的分层组装以及Far复合物在TORC 2信号传导中ER定位的功能。背景：Far 3 -7-8-9-10-11复合物是酵母纹状体蛋白相互作用磷酸酶和激酶（STRIPAK）复合物的一部分，介导雷帕霉素复合物2（TORC 2）信号传导的靶点。Far 3 -7-8-9-10-11复合物遵循内质网（ER）的分层组装。结论：Far 9的ER定位是TORC 2信号转导中最佳功能所必需的。
Target of rapamycin signaling is a conserved, essential pathway integrating nutritional cues with cell growth and proliferation. The target of rapamycin kinase exists in two distinct complexes, TORC1 and TORC2. It has been reported that protein phosphatase 2A (PP2A) and the Far3-7-8-9-10-11 complex (Far complex) negatively regulate TORC2 signaling in yeast. The Far complex, originally identified as factors required for pheromone-induced cell cycle arrest, and PP2A form the yeast counterpart of the STRIPAK complex, which was first isolated in mammals. The cellular localization of the Far complex has yet to be fully characterized. Here, we show that the Far complex localizes to the endoplasmic reticulum (ER) by analyzing functional GFP-tagged Far proteinsin vivo. We found that Far9 and Far10, two homologous proteins each with a tail-anchor domain, localize to the ER in mutant cells lacking the other Far complex components. Far3, Far7, and Far8 form a subcomplex, which is recruited to the ER by Far9/10. The Far3-7-8- complex in turn recruits Far11 to the ER. Finally, we show that the tail-anchor domain of Far9 is required for its optimal function in TORC2 signaling. Our study reveals tiered assembly of the yeast Far complex at the ER and a function for Far complex's ER localization in TORC2 signaling.Background: The Far3-7-8-9-10-11 complex, part of the yeast striatin-interacting phosphatase and kinase (STRIPAK) complex, mediates target of rapamycin complex 2 (TORC2) signaling.Results: The Far3-7-8-9-10-11 complex follows tiered assembly at the endoplasmic reticulum (ER).Conclusion: ER localization of Far9 is required for optimal function in TORC2 signaling.Significance: Our study provides insights into the organization of the yeast STRIPAK complex.