Golgi sorting regulates organization and activity of GPI proteins at apical membranes

Paladino, Simona; Lebreton, Stéphanie; Tivodar, Simona; Formiggini, Fabio; Ossato, Giulia; Gratton, Enrico; Tramier, Marc; Coppey-Moisan, Maïté; Zurzolo, Chiara

doi:10.1038/nchembio.1495

Cited by 43 publications

(104 citation statements)

References 53 publications

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“…Oligomerization has been proposed to facilitate GPI-AP segregation from other secretory proteins and to promote the coalescence of small lipid domains into larger and more stable domains that would favor vesicle budding from the TGN ( 68 ). In polarized epithelial cells, the oligomerization-based sorting mechanism of GPI-APs in the Golgi acquires a tremendous physiological relevance because it regulates both their organization and function at the apical membrane ( 75 ). N-glycosylation has been shown to be additionally required for apical delivery of GPI-APs, as well as other apically-targeted glycoproteins, suggesting an involvement of a lectin receptor-based mechanism ( 76 ).…”

Section: Discussionmentioning

confidence: 99%

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

Muñiz

Riezman

2016

Journal of Lipid Research

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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

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Section: Discussionmentioning

confidence: 99%

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

Muñiz

Riezman

2016

Journal of Lipid Research

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“…Interestingly, Golgi homoclustering not only mediates apical sorting of GPI‐APs but it is also required for their subsequent organization at the apical PM . Specifically, it has been shown that newly arrived homoclusters coalesce in heteroclusters (containing at least two different GPI‐AP species) that are sensitive to cholesterol depletion (Fig. ).…”

Section: Clustering Of Gpi‐aps In the Golgi Regulates Apical Sortingmentioning

confidence: 99%

“…Conversely, once formed, GPI‐AP homoclusters become insensitive to cholesterol depletion. Current data suggest that both protein–lipid and protein–protein interactions are involved in the formation and stabilization of GPI‐AP clusters . Although the biochemical nature of the interactions that determine apical GPI‐AP clustering prior to their apical sorting are not totally clear, the bulk of the evidence point out on the integrated action of the protein ectodomain and the GPI anchor together with the requirement of a favourable lipid environment (i.e., need of threshold levels of cholesterol in the Golgi membranes).…”

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confidence: 99%

“…Golgi GPI‐AP homoclusters are required for the subsequent organization of these proteins in larger cholesterol‐dependent clusters formed by multiple GPI‐AP species (heteroclusters) at the apical PM, of polarized epithelial cells . Thus, this clustered organization is achieved only in fully polarized cells when the sorting mechanism in the Golgi is active . Strikingly, this clustered organization appears to regulate also the activity of GPI‐APs at the PM, so that only when the GPI‐APs are correctly sorted they are organized in functional clusters at the surface.…”

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

2019

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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.

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“…Although fibroblasts and polarized epithelial cells might share this requirement, we have recently shown that the plasma membrane organization of GPI-APs is considerably different between fibroblasts and epithelial cells. Furthermore, we find that, in polarized epithelial cells, the oligomerization-based sorting mechanism of GPI-APs in the Golgi appears to regulate both their organization and function at the apical membrane (Paladino et al, 2014).…”

Section: Mechanism Of Oligomerizationmentioning

confidence: 97%

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

Muñiz

Zurzolo

2014

Journal of Cell Science

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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.

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Golgi sorting regulates organization and activity of GPI proteins at apical membranes

Cited by 43 publications

References 53 publications

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

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

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

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

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