Sorting of GPI-anchored proteins from yeast to mammals – common pathways at different sites?

Abstract

Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are luminal secretory cargos that are attached by a post-translational glycolipid modification, the GPI anchor, to the external leaflet of the plasma membrane. GPI-APs are conserved among eukaryotes and possess many diverse and vital functions for which the GPI membrane attachment appears to be essential. The presence of the GPI anchor and its subsequent modifications along the secretory pathway confer to the anchored proteins unique trafficking properties that make GPIAPs an exceptional system to study mechanisms of sorting. In this Commentary, we discuss the recent advances in the field of GPI-AP sorting focusing on the mechanisms operating at the level of the exit from the ER and from the trans-Golgi network (TGN), which take place, respectively, in yeast and in polarized mammalian cells. By considering the similarities and differences between these two sorting events, we present unifying principles that appear to work at different sorting stations and in different organisms.

Thematic Review Series: Glycosylphosphatidylinositol (GPI) Anchors: Biochemistry and Cell Biology Biosynthesis of GPI-anchored proteins: special emphasis on GPI lipid remodeling

“…Mechanisms of apical sorting of GPI-APs have been intensively studied ( 10 ). Oligomerization of GPI-APs in the trans-Golgi network seems to be critical for selective transport to the apical surface [see detailed discussion in a recent review ( 82,83 )]. …”

Glycosylphosphatidylinositol (GPI) modification serves as a primary plasmodesmal targeting signal

“…In addition, proteomic analysis of sterol-enriched detergent-resistant membranes in Arabidopsis revealed that GPI-APs are overrepresented in those membranes (Kierszniowska et al, 2009). Indeed, more detailed studies in mammalian cells show that an association with membrane microdomains is a general property of GPI-APs; however, the pattern of their lateral organization at the cell surface is determined by additional signals associated with protein ectodomain, cell type, and physiological state (Muñiz and Zurzolo, 2014;Paladino et al, 2015;Saha et al, 2016). Expression of BG_pap and PDCB1 with their ectodomains resulted in a higher accumulation at Pd, but not at the PM, compared with GPI-anchored mCitrine (Fig.…”

“…7), which again indicates that Pd exclusion most likely occurs prior to PM and Pd localization. Studies in mammalian cells have shown that the sorting of different groups of GPI-APs occurs at the trans-Golgi network (TGN; Muñiz and Zurzolo, 2014). In polarized human and Madin-Darby canine kidney epithelial cells, the GPI-APs that target to the microdomain-rich apical PM segregate from the basolateral GPI-APs by forming large microdomain-rich clusters at the TGN (Muñiz and Zurzolo, 2014).…”

“…Studies in mammalian cells have shown that the sorting of different groups of GPI-APs occurs at the trans-Golgi network (TGN; Muñiz and Zurzolo, 2014). In polarized human and Madin-Darby canine kidney epithelial cells, the GPI-APs that target to the microdomain-rich apical PM segregate from the basolateral GPI-APs by forming large microdomain-rich clusters at the TGN (Muñiz and Zurzolo, 2014). It was shown that the apical GPI-APs indeed arrive at the PM as immobile clusters that form in the Golgi network (Hannan et al, 1993).…”

“…Such remodeling is crucial for the sorting of GPI-APs in the secretory pathway and the subsequent lateral heterogeneity at the PM (Kinoshita, 2015). In particular, the addition of saturated fatty acid chains to the lipid moiety of the anchor leads to the enriched accumulation of GPI-APs in the PM microdomains, also termed lipid rafts (Muñiz and Zurzolo, 2014). In Arabidopsis (Arabidopsis thaliana), GPI modification has been predicted for 210 proteins of diverse functions at the PM or the cell wall or both (Borner et al, 2002).…”