Clustering in the Golgi apparatus governs sorting and function of GPI‐APs in polarized epithelial cells

Abstract

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.

Novel insights into the function of CD24: A driving force in cancer

“…In polarized epithelial cells, protein homooligomerization is a key step determining the apical sorting of GPI‐anchored proteins 20 . The presence of both lipid anchor and protein portions confers unique trafficking features to these proteins.…”

“…The presence of both lipid anchor and protein portions confers unique trafficking features to these proteins. This allows them to partition into membrane microdomains enriched in cholesterol and sphingolipids (lipid rafts) 20,21 …”

“…The study of Kadmon et al suggested that mouse CD24 (ie, nectadrin) is a cell adhesion glycoprotein exhibiting homophilic binding 34 . It is possible that this type of interaction is carbohydrate‐mediated and reflects the ability of GPI‐anchored proteins to cluster in lipid rafts 20 . In mouse brain, CD24 can interact in a carbohydrate‐dependent manner with the neural adhesion molecule L1CAM (CD171), leading to the inhibition of neurite growth and altered L1CAM signaling 35‐37 …”

“…On the other hand, it is clear that just the presence of CD24 confers distinct features on the expressing cells that are not shared by nonexpressing cells. The presence of CD24 at the cell surface may lead to homogenous clustering of membrane rafts caused by lipid anchor modifications and/or glycosylation or affects raft endocytosis 19,20,64 …”

The Golgi complex: 120 years and it doesn't show

“…The second part of the 2018 Golgi meeting and this special issue maintain the above focus on the role of signalling in endomembranes function, but also emphasize more on the cross‐regulation concept. Such examples of cross‐regulation include: the lysosome‐based signaling and its impact on nuclear functions ; the endomembrane‐based signaling and various types of stress, either oxidative or nutritional ; the regulation of ion homeostasis by the Golgi, with a talk dedicated to a disease (the Wilson syndrome) due to a defect in copper metabolism ; and the role of calcium in the apical secretion of GPI‐linked proteins . Another exciting theme in the 2018 Golgi meeting session on interorganellar signaling and coordination with complex cellular responses was the signaling mechanisms linking the Golgi fragmentation process to mitotic entry.…”