Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain.
Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain; Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain.
Semin Cell Dev Biol. 2018 Nov;83:22-28. doi: 10.1016/j.semcdb.2018.02.021. Epub 2018 Feb 28.
It is usually assumed that eukaryotic cells secrete only proteins that contain a signal sequence for Sec61 mediated translocation into the lumen of endoplasmic reticulum (ER). Surprisingly however, many proteins, such as superoxide dismutase (SOD)1, acyl-CoA binding protein (Acb1), interleukin 1β, fibroblast growth factor 2 and the adipokine Unpaired2, to name a few, are secreted even though they lack a signal sequence. The discovery that these proteins are secreted has presented a new challenge and we describe here a common pathway by which SOD1 and Acb1 are specifically secreted upon nutrient starvation. Their secretion follows a type III unconventional pathway, requiring the exposure of a di-acidic motif, which we propose promotes their capture into a membrane compartment called CUPS (compartment for unconventional protein secretion). We suggest that CUPS, composed of membranes derived from the Golgi apparatus and endosomes, serves as a major sorting station prior to release of SOD1 and Acb1 into the extracellular space. The trafficking of these signal sequence lacking proteins therefore has functional similarities to conventional protein secretion in that they rely on membrane bounded compartments for their sorting and transport, but bypass the need of Sec61 for translocating into the ER and COPII and COPI for their intracellular transfers. This review is part of a Special Issue of SCDB on "unconventional protein secretion" edited by Walter Nickel and Catherine Rabouille.
通常认为，真核细胞只分泌含有信号序列的蛋白质，该信号序列用于 Sec61 介导的易位进入内质网（ER）腔。然而，令人惊讶的是，许多蛋白质，如超氧化物歧化酶（SOD）1、酰基辅酶 A 结合蛋白（Acb1）、白细胞介素 1β、成纤维细胞生长因子 2 和脂肪因子 Unpaired2 等，尽管它们缺乏信号序列，但仍被分泌。这些蛋白质被分泌的发现提出了一个新的挑战，我们在这里描述了 SOD1 和 Acb1 在营养饥饿时被特异性分泌的常见途径。它们的分泌遵循一种 III 型非经典途径，需要暴露二酸性基序，我们提出该基序促进它们被捕获到称为 CUPS（非常规蛋白分泌的隔室）的膜隔室中。我们认为，由高尔基体和内体衍生的膜组成的 CUPS 在 SOD1 和 Acb1 释放到细胞外空间之前充当主要分拣站。这些缺乏信号序列的蛋白质的运输因此与传统的蛋白质分泌具有功能相似性，因为它们依赖于膜结合隔室进行分拣和运输，但不需要 Sec61 易位进入 ER 和 COPII 和 COPI 进行细胞内转移。这篇综述是由 Walter Nickel 和 Catherine Rabouille 编辑的 SCDB 特刊“非常规蛋白分泌”的一部分。
