Genomewide Analysis Reveals Novel Pathways Affecting Endoplasmic Reticulum Homeostasis, Protein Modification and Quality Control
Genomewide Analysis Reveals Novel Pathways Affecting Endoplasmic Reticulum Homeostasis, Protein Modification and Quality Control
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DOI：
10.1534/genetics.109.101105
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发表时间：
2009-07-01
期刊：
影响因子：
3.3
通讯作者：
Miller, Elizabeth A.
中科院分区：
文献类型：
--
作者：
Copic, Alenka;Dorrington, Mariana;Miller, Elizabeth A.
为了获得新的机制洞察ER稳态和分泌蛋白的生物发生，我们筛选了全基因组范围内收集的酵母突变体有缺陷的细胞内滞留的ER伴侣，Kar2p。我们确定了87 Kar2p分泌菌株，包括一些已知的分泌蛋白修饰和分选的组件。对73个非必需的Kar2p保留突变体的进一步表征揭示了许多新的基因产物在蛋白糖基化、GPI锚定附着、ER质量控制、逃逸的ER驻留物的中间恢复中的作用。这些突变体的一个子集，需要ER检索，包括GET复合物和两种新的蛋白质，可能在膜插入的尾锚定蛋白的功能相似。最后，组蛋白的变体，Htz1p，及其乙酰化状态似乎在维持ER检索途径中发挥重要作用，这表明染色质重塑和ER稳态之间存在惊人的联系。
To gain new mechanistic insight into ER homeostasis and the biogenesis of secretory proteins, we screened a genomewide collection of yeast mutants for defective intracellular retention of the ER chaperone, Kar2p. We identified 87 Kar2p-secreting strains, including a number of known components in secretory protein modification and sorting. Further characterization of the 73 nonessential Kar2p retention mutants revealed roles for a number of novel gene products in protein glycosylation, GPI-anchor attachment, ER quality control, Mid retrieval of escaped ER residents. A subset of these mutants, required for ER retrieval, included the GET complex and two novel proteins that likely function similarly in membrane insertion of tail-anchored proteins. Finally, the variant histone, Htz1p, and its acetylation state seem to play an important role in maintaining ER retrieval pathways, suggesting a surprising link between chromatin remodeling and ER homeostasis.