Trafficking and Membrane Organization of GPI-Anchored Proteins in Health and Diseases

Paladino, Simona; Lebreton, Stéphanie; Zurzolo, Chiara

doi:10.1016/bs.ctm.2015.03.006

Cited by 36 publications

(36 citation statements)

References 171 publications

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“…While in yeast the ER is the site where GPI‐APs are sorted from the other secretory proteins , in mammals the Golgi complex, and in particular the TGN, is the major sorting station . In polarized epithelial cells, apical and basolateral proteins are sorted and incorporated into distinct vesicles at the TGN level upon recognition of specific apical or basolateral signals .…”

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

confidence: 99%

“…Several proteins have been implicated in regulating the apical transport of raft‐associated transmembrane and GPI‐linked proteins (such as VIP17/MAL, caveolins, annexins, galectins), but they do not seem to be specific for GPI‐APs and their mechanistic role is not completely clear . Among them, galectin‐4 could favour the segregation of apical rafts‐associated proteins from not associated apical and basolateral cargoes by binding sulfatides with long chain‐hydroxylated fatty acids and clustering glycosphingolipid platforms .…”

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

confidence: 99%

“…Besides post‐translational protein modifications, recent studies have highlighted that GPI anchor remodelling has profound effects on their traffic along the secretory pathway. Moreover, GPI‐APs partition with cholesterol and sphingolipids (SPLs) enriched membrane microdomains that could influence both their trafficking and their surface organization .…”

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confidence: 99%

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

confidence: 99%

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

confidence: 99%

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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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“…This also extends the possibility of making progress in our fundamental understanding of the biology of GPI-related diseases ( 134 ).…”

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confidence: 99%

GPI-anchored protein organization and dynamics at the cell surface

Saha

Anilkumar

Mayor

2016

Journal of Lipid Research

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of the protein called glycosylphosphatidylinositol (GPI)-anchored proteins. The basic structure of a GPI-anchored protein consists of phosphatidylinositol (PI) linked to an unusual non-N -acetyl glucosamine, which, in turn, is linked to three mannose residues followed by an ethanolamine covalently linked to the protein via an amide linkage (EtNP-6Man ␣ 1-2Man ␣ 1-6Man ␣ 1-4GlcN ␣ 1-6 myo inositolphospholipid, Fig. 1A ). Depending on the species and functional context, there may exist variations in the side chain associated with the glycan core. These have been summarized in ( 1 ). The lipid moiety is necessary for the incorporation of GPI-anchored proteins into so-called lipid rafts/microdomains ( 2, 3 ), which can serve as a sorting station for a number of cell signaling molecules, thereby functioning as a reaction center. GPI-anchored proteins can exist in different forms depending on the context and the tissue in which they are expressed. Alternate splicing can cause the same protein to exhibit TM, soluble, or GPI-anchored forms; for example, neural cell adhesion molecule (NCAM) can exist in its GPI-anchored and soluble form when expressed in muscles; whereas, it takes up a TM form instead of the soluble form in brain. GPI anchoring of proteins occurs at the luminal face of The plasma membrane of the cell is comprised of a diverse set of proteins, many of which are transmembrane (TM) proteins spanning the entire bilayer, but a significant proportion of proteins are also lipid tethered, containing a complex glycan core attached to the C terminus

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

2016

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Plasmodesmata (Pd) are membranous channels that serve as a major conduit for cell-to-cell communication in plants. The Pdassociated b-1,3-glucanase (BG_pap) and CALLOSE BINDING PROTEIN1 (PDCB1) were identified as key regulators of Pd conductivity. Both are predicted glycosylphosphatidylinositol-anchored proteins (GPI-APs) carrying a conserved GPI modification signal. However, the subcellular targeting mechanism of these proteins is unknown, particularly in the context of other GPI-APs not associated with Pd. Here, we conducted a comparative analysis of the subcellular targeting of the two Pd-resident and two unrelated non-Pd GPI-APs in Arabidopsis (Arabidopsis thaliana). We show that GPI modification is necessary and sufficient for delivering both BG_pap and PDCB1 to Pd. Moreover, the GPI modification signal from both Pd-and non-Pd GPI-APs is able to target a reporter protein to Pd, likely to plasma membrane microdomains enriched at Pd. As such, the GPI modification serves as a primary Pd sorting signal in plant cells. Interestingly, the ectodomain, a region that carries the functional domain in GPI-APs, in Pd-resident proteins further enhances Pd accumulation. However, in non-Pd GPI-APs, the ectodomain overrides the Pd targeting function of the GPI signal and determines a specific GPI-dependent non-Pd localization of these proteins at the plasma membrane and cell wall. Domainswap analysis showed that the non-Pd localization is also dominant over the Pd-enhancing function mediated by a Pd ectodomain. In conclusion, our results indicate that segregation between Pd-and non-Pd GPI-APs occurs prior to Pd targeting, providing, to our knowledge, the first evidence of the mechanism of GPI-AP sorting in plants.

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Trafficking and Membrane Organization of GPI-Anchored Proteins in Health and Diseases

Cited by 36 publications

References 171 publications

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

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

GPI-anchored protein organization and dynamics at the cell surface

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

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