Unité de Trafic Membranaire et Pathogénèse, Institut Pasteur, Paris, France.
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Naples, Italy.
FEBS Lett. 2019 Sep;593(17):2351-2365. doi: 10.1002/1873-3468.13573. Epub 2019 Sep 2.
Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are lipid APs attached to the extracellular leaflet of the plasma membrane (PM) via a glycolipid anchor. GPI-APs are commonly associated with cholesterol- and sphingolipid-enriched membrane microdomains. These microdomains help regulating various biological activities, by segregating different proteins and lipids in (nanoscale) membrane compartments. In fibroblasts, GPI-APs form actin- and cholesterol-dependent nanoclusters directly at the PM. In contrast, in polarized epithelial cells GPI-APs cluster in the Golgi apparatus, the major protein-sorting hub for the secretory pathway. Golgi clustering is required for the selective sorting of GPI-APs to the apical PM domain, but also regulates their organization and biological activities at the cell surface. In this review, we discuss recent advances in our understanding of the mechanism of GPI-AP sorting to the apical membrane. We focus on the roles of the protein moiety and lipids in the regulation of the clustering of GPI-APs in the Golgi apparatus.
糖基磷脂酰肌醇锚定蛋白（GPI-APs）通过糖脂锚附着在质膜（PM）的细胞外小叶。GPI-APs 通常与富含胆固醇和鞘脂的膜微区相关。这些微区通过在（纳米级）膜隔室中隔离不同的蛋白质和脂质，有助于调节各种生物活性。在成纤维细胞中，GPI-APs 在质膜上直接形成肌动蛋白和胆固醇依赖性的纳米簇。相比之下，在极化的上皮细胞中，GPI-APs 在高尔基器中聚集，高尔基器是分泌途径的主要蛋白质分拣中心。高尔基器的聚类对于 GPI-APs 到顶质膜域的选择性分拣是必需的，但也调节它们在细胞表面的组织和生物活性。在这篇综述中，我们讨论了我们对 GPI-AP 分拣到顶质膜机制的理解的最新进展。我们重点讨论了蛋白质部分和脂质在调节高尔基器中 GPI-AP 聚类中的作用。
