Trafficking of glycosylphosphatidylinositol anchored proteins from the endoplasmic reticulum to the cell surface

Abstract

This article is available online at http://www.jlr.org vesicular traffi cking events ( 1 ). Many secretory proteins that are delivered to the cell surface, including a wide diversity of receptors, adhesion molecules, and enzymes, are attached to the external leafl et of the plasma membrane via a glycosylphosphatidylinositol (GPI) anchor ( 2 ). The core structure of the GPI anchor precursor is largely conserved in evolution and consists of a phospholipid moiety (acylphosphatidylinositol) with a glycan backbone [Man4-(EtNP)Man3-(EtNP)Man2-(EtNP)Man1-GlcN], where EtNP is a side-branch ethanolamine-phosphate, Man is mannose (the numbers represent the positions of the Man in the anchor), and GlcN is glucosamine). Once the GPI anchor precursor has been made by a series of sequential reactions at the ER membrane, it is then attached en bloc in the ER lumen by a GPI-transamidase complex to newly synthesized proteins containing a GPI attachment signal sequence at their C terminus. Immediately after attachment to the protein, the structure of the lipid and glycan parts of the GPI anchor are modifi ed by several remodeling enzymes ( 3 ). This remodeling process converts the GPI anchor into a transport signal that actively promotes the ER export of GPI-anchored proteins (GPI-APs) to the Golgi apparatus, from where they are subsequently routed to their functional site of residence, the plasma membrane.The presence of the GPI anchor confers to GPI-APs a unique mode of membrane association within the lumen of secretory organelles that leads them to be transported The eukaryotic secretory pathway is responsible for the synthesis and delivery of correctly assembled proteins from the endoplasmic reticulum (ER) to their fi nal functional destination, the extracellular media, the plasma membrane, or the endocytic/secretory membrane system. The vast majority of proteins are transported by a series of specifi c Abstract In eukaryotes, many cell surface proteins are attached to the plasma membrane via a glycolipid glycosylphosphatidylinositol (GPI) anchor. GPI-anchored proteins (GPI-APs) receive the GPI anchor as a conserved posttranslational modifi cation in the lumen of the endoplasmic reticulum (ER). After anchor attachment, the GPI anchor is structurally remodeled to function as a transport signal that actively triggers the delivery of GPI-APs from the ER This work was supported by grants

Arabidopsis thaliana FLA4 functions as a glycan‐stabilized soluble factor via its carboxy‐proximal Fasciclin 1 domain

“…As an initial clue we observed that in growing roots the localization of the F4C∆Fas1‐1 protein in endosomes was dramatically increased compared with the mostly plasma membrane localized protein full‐length F4C. Because N‐ glycosylation is involved in the apical sorting of mammalian GPI‐APs (Muniz and Riezman, ), one could speculate that the highly N‐ glycosylated Fas1‐1 domain might be required for the efficient secretion of FLA4. However, several observations argue against this interpretation.…”

Glucosylhydroxyceramides Modulate Secretion Machinery of a Subset of Plasmodesmata Proteins and a Change in the Callose Accumulation

“…Since myriocin-, FB1-, PDMP-, and D609-suppressed GlcHCers level only disrupted the subcellular localization of the GPI-anchored PD proteins and not that of PDLP1 protein, we hypothesized that the GPI-anchored PdBG2 and PDLP1 proteins might use different cargo machinery in a GlcHCers-enriched vesicle-dependent manner. The secretory pathways for GPI-anchored proteins and non GPI-anchored transmembrane or secretory proteins are distinct in yeast and mammalian cells (Funato and Riezman, 2001; Muniz et al, 2001; Watanabe et al, 2008; Castillon et al, 2009; Rivier et al, 2010; Muniz and Zurzolo, 2014; Paladino et al, 2014; Muniz and Riezman, 2016). During protein secretion in yeast, GPI-anchored proteins are segregated from other proteins and delivered to their final destination by SL-enriched vesicles (Silva et al, 2007; Kajiwara et al, 2008; Loizides-Mangold et al, 2012).…”

Characterization of Glycosylphosphatidylinositol Biosynthesis Defects by Clinical Features, Flow Cytometry, and Automated Image Analysis

“…Of note is, however, that an assessment of the GPI-AP expression levels seems more sensitive in the fibroblasts than in blood cells [23]. This might also be related to the trafficking pathways of GPI-APs through ER and Golgi that differ for cell types and substrates [66, 67].…”