UPS - Unconventional Protein Secretion

已经描述了两种类型的非经典蛋白质转运到真核细胞的细胞表面，这些过程统称为“非常规蛋白质分泌”（UPS）。第一种类型以完整的膜蛋白为代表，可以以高尔基独立的方式到达细胞表面。第二种类型是由可溶性分泌蛋白使用，这些蛋白在不涉及内质网（ER）和高尔基体系统的情况下离开细胞。虽然整合素是通过非常规方式运输的膜蛋白的一个例子，但可溶性非常规分泌蛋白的类别包括白细胞介素（IL）家族成员、成纤维细胞生长因子（FGF）、巨噬细胞迁移抑制因子（MIF）、半乳糖凝集素和酰基辅酶a结合蛋白，这些大分子从细胞分泌，调节免疫反应、细胞生长和分化以及血管生成。这些显然是非常重要的蛋白质，因此了解它们的分泌机制是至关重要的。我们建议建立一个由欧洲领先的实验室组成的网络，这些实验室将在分子水平上合作阐明这些“非常规的蛋白质分泌途径”。我们将使用先进的技术，如iTRAQ和SILAC蛋白质组学，以及使用RNA干扰进行全基因组筛选，以确定必需成分，并揭示调节非常规蛋白质分泌的机制。

Two types of non-classical protein transport to the cell surface of eukaryotic cells have been described, processes that collectively have been termed 'Unconventional Protein Secretion' (UPS). The first type is represented by integral membrane proteins that can reach the cell surface in a Golgi-independent manner. The second type is being used by soluble secretory proteins that exit cells without any involvement of the endoplasmic reticulum (ER) and the Golgi system. While integrins are an example for membrane proteins transported by unconventional means, the class of soluble unconventional secretory proteins includes interleukin (IL) family members, fibroblast growth factors (FGF), macrophage migration inhibitory factor (MIF), galectins and acyl-CoA binding protein, macromolecules that are secreted from cells to regulate the immune response, cell growth and differentiation as well as angiogenesis. These are clearly very important proteins and an understanding of their mechanism of secretion is therefore of fundamental importance. We propose a network of leading European laboratories that will collaborate to elucidate these “unconventional pathways of protein secretion” at the molecular level. We will use advanced techniques such as iTRAQ and SILAC proteomics as well as genome-wide screening using RNA interference to identify essential components and to reveal the mechanisms regulating unconventional protein secretion.