Asymmetric Tethering of Flat and Curved Lipid Membranes by a Golgin

Drin, Guillaume; Morello, Vincent; Casella, Jean-François; Gounon, Pierre; Antonny, Bruno

doi:10.1126/science.1155821

Cited by 165 publications

(208 citation statements)

References 23 publications

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“…Phase contrast microscopy of precipitated samples showed branching objects of irregular shapes apparently formed of smaller clusters (Figure 2.) which resembled electron micrographs of liposomal aggregates seen earlier [13].…”

Section: Pegylated Liposomes Can Be Precipitated By Ammonium Sulfatesupporting

confidence: 78%

Aggregation of PEGylated liposomes driven by hydrophobic forces

Bozó

Mészáros

Mihály

et al. 2016

Colloids and Surfaces B: Biointerfaces

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2 Graphical Abstract 3 Highlights Kosmotropes induce the aggregation and fusion of PEG-liposomes.  The effect depends on both the kosmotrope and PEG concentration.  Aggregation is reversible under certain conditions.  Kosmotropes lead to a dehydration-related conformational change of the PEG polymer.  The likely driving force behind aggregation is the hydrophobic effect. 4 ABSTRACTPolyethylene glycol (PEG) is widely used to sterically stabilize liposomes and improve the pharmacokinetic profile of drugs, peptides and nanoparticles. Here we report that ammonium sulfate (AS) can evoke the aggregation of PEGylated vesicles in a concentration-dependent manner. Liposomes with 5 mol% PEG were colloidally stable at AS concentrations up to 0.7 mM, above which they precipitated and formed micron-size aggregates with irregular shape. While aggregation was reversible up to 0.9 M of AS, above 1 M fusion occurred, which irreversibly distorted the size distribution. Zeta potential of liposomes markedly increased from -71±2.5 mV to 2±0.5 mV upon raising the AS concentration from 0 to 0.1 M, but no considerable increase was seen during further AS addition, showing that the aggregation is independent of surface charge. There was no aggregation in the absence of the PEG chains, and increasing PEG molar % shifted the aggregation threshold to lower AS concentrations. Changes in the FTIR spectral features of PEGylated vesicles suggest that AS dehydrates PEG chains. Other kosmotropic salts also led to aggregation, while chaotropic salts did not, which indicates a general kosmotropic phenomenon. The driving force behind aggregation is likely to be the hydrophobic effect due to salting out the polymer similarly to what happens during protein purification or Hydrophobic Interaction Chromatography. Since liposome aggregation and fusion may result in difficulties during formulation and adverse reaction upon application, the phenomena detailed in this paper may have both technological and therapeutical consequences.

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Section: Pegylated Liposomes Can Be Precipitated By Ammonium Sulfatesupporting

confidence: 78%

Aggregation of PEGylated liposomes driven by hydrophobic forces

Bozó

Mészáros

Mihály

et al. 2016

Colloids and Surfaces B: Biointerfaces

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“…GMAP-210 associates with Golgi membranes through its C-terminal GRIP-related Arf-binding (GRAB) domain, which binds specifically to Arf1-GTP (Gillingham et al, 2004). The Nterminus of GMAP-210 contains an ALPS motif that binds to the highly curved membranes of early Golgi vesicles (Cardenas et al, 2009;Drin et al, 2008). ArfGAP1 is also recruited specifically to highly curved membranes through its ALPS motifs, and so will hydrolyze GTP on Arf1 only on curved surfaces, not on flat ones.…”

Section: Arf Effectors In Vesicle Traffickingmentioning

confidence: 99%

“…ArfGAP1 is also recruited specifically to highly curved membranes through its ALPS motifs, and so will hydrolyze GTP on Arf1 only on curved surfaces, not on flat ones. In this way, a self-organizational module is established that will specifically tether a vesicle to a flat Golgi membrane in a dynamic manner (Drin et al, 2008). The perception of golgins as tentacles, having one end anchored to flat Golgi cisternae and the other extending out to capture vesicles by various mechanisms, has led to the proposal that golgins form a tentacular cytomatrix around Golgi membranes to facilitate vesicle flow to and through the Golgi (Munro, 2011).…”

Section: Arf Effectors In Vesicle Traffickingmentioning

confidence: 99%

Arfs at a Glance

Jackson

Bouvet

2014

Journal of Cell Science

116

117

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The Arf small G proteins regulate protein and lipid trafficking in eukaryotic cells through a regulated cycle of GTP binding and hydrolysis. In their GTP-bound form, Arf proteins recruit a specific set of protein effectors to the membrane surface. These effectors function in vesicle formation and tethering, non-vesicular lipid transport and cytoskeletal regulation. Beyond fundamental membrane trafficking roles, Arf proteins also regulate mitosis, plasma membrane signaling, cilary trafficking and lipid droplet function. Tight spatial and temporal regulation of the relatively small number of Arf proteins is achieved by their guanine nucleotideexchange factors (GEFs) and GTPase-activating proteins (GAPs), which catalyze GTP binding and hydrolysis, respectively. A unifying function of Arf proteins, performed in conjunction with their regulators and effectors, is sensing, modulating and transporting the lipids that make up cellular membranes. In this Cell Science at a Glance article and the accompanying poster, we discuss the unique features of Arf small G proteins, their functions in vesicular and lipid trafficking in cells, and how these functions are modulated by their regulators, the GEFs and GAPs. We also discuss how these Arf functions are subverted by human pathogens and disease states.

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“…In eukaryotic cells, a number of dedicated endogenous proteins seem to be able to increase membrane curvature and curl up intracellular membranes to tubules and vesicles (21)(22)(23). A foreign bacterial (Shiga) toxin can achieve similar features (24).…”

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confidence: 99%

Massive Formation of Intracellular Membrane Vesicles in Escherichia coli by a Monotopic Membrane-bound Lipid Glycosyltransferase

Eriksson

Wessman

et al. 2009

Journal of Biological Chemistry

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The morphology and curvature of biological bilayers are determined by the packing shapes and interactions of their participant molecules. Bacteria, except photosynthetic groups, usually lack intracellular membrane organelles. Strong overexpression in Escherichia coli of a foreign monotopic glycosyltransferase (named monoglycosyldiacylglycerol synthase), synthesizing a nonbilayer-prone glucolipid, induced massive formation of membrane vesicles in the cytoplasm. Vesicle assemblies were visualized in cytoplasmic zones by fluorescence microscopy. These have a very low buoyant density, substantially different from inner membranes, with a lipid content of >60% (w/w). Cryo-transmission electron microscopy revealed cells to be filled with membrane vesicles of various sizes and shapes, which when released were mostly spherical (diameter ≈100 nm). The protein repertoire was similar in vesicle and inner membranes and dominated by the glycosyltransferase. Membrane polar lipid composition was similar too, including the foreign glucolipid. A related glycosyltransferase and an inactive monoglycosyldiacylglycerol synthase mutant also yielded membrane vesicles, but without glucolipid synthesis, strongly indicating that vesiculation is induced by the protein itself. The high capacity for membrane vesicle formation seems inherent in the glycosyltransferase structure, and it depends on the following: (i) lateral expansion of the inner monolayer by interface binding of many molecules; (ii) membrane expansion through stimulation of phospholipid synthesis, by electrostatic binding and sequestration of anionic lipids; (iii) bilayer bending by the packing shape of excess nonbilayer-prone phospholipid or glucolipid; and (iv) potentially also the shape or penetration profile of the glycosyltransferase binding surface. These features seem to apply to several other proteins able to achieve an analogous membrane expansion.

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Asymmetric Tethering of Flat and Curved Lipid Membranes by a Golgin

Cited by 165 publications

References 23 publications

Aggregation of PEGylated liposomes driven by hydrophobic forces

Aggregation of PEGylated liposomes driven by hydrophobic forces

Arfs at a Glance

Massive Formation of Intracellular Membrane Vesicles in Escherichia coli by a Monotopic Membrane-bound Lipid Glycosyltransferase

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