A striking quality control subcompartment in Saccharomyces cerevisiae:: The endoplasmic reticulum-associated compartment
A striking quality control subcompartment in Saccharomyces cerevisiae:: The endoplasmic reticulum-associated compartment
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DOI：
10.1091/mbc.e03-07-0546
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发表时间：
2004-02-01
影响因子：
3.3
通讯作者：
Michaelis, S
中科院分区：
文献类型：
--
作者：
Huyer, G;Longsworth, GL;Michaelis, S
新生分泌蛋白和膜蛋白的折叠由内质网 (ER) 质量控制系统监测。错误折叠的蛋白质保留在内质网中，并可以通过内质网相关的降解来去除。作为酵母中多发膜蛋白内质网质量控制的模型，我们一直在研究 Ste6p 的突变形式。在这里，我们鉴定了 Ste6p 的错误定位突变形式，这些突变形式诱导正常细胞中不存在的突出结构的形成和定位。我们根据荧光和电子显微镜观察到的这些结构与内质网的并置和连接，将这些结构命名为内质网相关区室 (ERAC)。 ERAC 似乎由管状囊泡结构网络组成。代表增殖的 ER 膜。除了正常的 ER 定位外，ERAC 中还存在驻留 ER 腔蛋白和膜蛋白，这表明它们进入 ERAC 没有障碍。然而，ERAC 中的 Ste6p 形式被排除在 ER 之外，并且不进入分泌途径；相反，它们最终会成为与内质网相关的降解的目标。 ERAC 的存在不会对通过 ER 的分泌蛋白运输产生不利影响，也不会导致未折叠蛋白反应的诱导。我们认为 ERAC 可能是错误折叠膜蛋白专门转移的位点，以免干扰正常的细胞功能。我们讨论了响应某些其他突变或未组装膜蛋白而形成的相关 ER 膜增殖可能与 ERAC 基本相似的可能性。
The folding of nascent secretory and membrane proteins is monitored by the endoplasmic reticulum (ER) quality control system. Misfolded proteins are retained in the ER and can be removed by ER-associated degradation. As a model for the ER quality control of multisparming membrane proteins in yeast, we have been studying mutant forms of Ste6p. Here, we identify mislocalized mutant forms of Ste6p that induce the formation of, and localize to, prominent structures that are absent in normal cells. We have named these structures ER-associated compartments (ERACs), based on their juxtaposition to and connection with the ER, as observed by fluorescence and electron microscopy. ERACs comprise a network of tubulo-vesicular structures that seem. to represent proliferated ER membranes. Resident ER lumenal and membrane proteins are present in ERACs in addition to their normal ER localization, suggesting there is no barrier for their entry into ERACs. However, the forms of Ste6p in ERACs are excluded from the ER and do not enter the secretory pathway; instead, they are ultimately targeted for ER-associated degradation. The presence of ERACs does not adversely affect secretory protein traffic through the ER and does not lead to induction of the unfolded protein response. We propose that ERACs may be holding sites to which misfolded membrane proteins are specifically diverted so as not to interfere with normal cellular functions. We discuss the likelihood that related ER membrane proliferations that form in response to certain other mutant or unassembled membrane proteins may be substantially similar to ERACs.