A Network of Cytosolic Factors Targets SRP-Independent Proteins to the Endoplasmic Reticulum
A Network of Cytosolic Factors Targets SRP-Independent Proteins to the Endoplasmic Reticulum
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DOI：
10.1016/j.cell.2013.02.003
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发表时间：
2013-02-28
期刊：
影响因子：
64.5
通讯作者：
Schuldiner, Maya
中科院分区：
文献类型：
--
作者：
Ast, Tslil;Cohen, Galit;Schuldiner, Maya
在真核生物中，转运到内质网（ER）是所有分泌蛋白和内膜蛋白生物合成的起始和关键步骤。ER插入可以通过充分表征的信号识别颗粒（SRP）依赖性途径或较少研究的SRP非依赖性易位途径发生。为了更好地理解SRP非依赖性途径的流行，我们系统地定义了酵母分泌组的易位依赖性。通过结合基于亲水性的分析和显微镜，我们发现，以前不受重视的部分酵母分泌组易位没有SRP的帮助。此外，我们验证了一个家庭的SRP-独立的底物糖基磷脂酰肌醇（GPI）锚定蛋白。通过研究这个家族，我们确定了ER靶向的决定因素，并发现了促进SRP非依赖性靶向和易位的胞质蛋白网络。这些发现突出了未被充分认识的SRP非依赖性易位的复杂性，这使得该途径能够有效地科普其广泛的底物通量。
Translocation into the endoplasmic reticulum (ER) is an initial and crucial biogenesis step for all secreted and endomembrane proteins in eukaryotes. ER insertion can take place through the well-characterized signal recognition particle (SRP)-dependent pathway or the less-studied route of SRP-independent translocation. To better understand the prevalence of the SRP-independent pathway, we systematically defined the translocational dependence of the yeast secretome. By combining hydropathy-based analysis and microscopy, we uncovered that a previously unappreciated fraction of the yeast secretome translocates without the aid of the SRP. Furthermore, we validated a family of SRP-independent substrates-the glycosylphosphatidylinositol (GPI)-anchored proteins. Studying this family, we identified a determinant for ER targeting and uncovered a network of cytosolic proteins that facilitate SRP-independent targeting and translocation. These findings highlight the underappreciated complexity of SRP-independent translocation, which enables this pathway to efficiently cope with its extensive substrate flux.