COPI buds 60-nm lipid droplets from reconstituted water–phospholipid–triacylglyceride interfaces, suggesting a tension clamp function

Thiam, Abdou Rachid; Antonny, Bruno; Wang, Jing; Delacotte, Jérôme; Wilfling, Florian; Walther, Tobias C.; Beck, Rainer; Rothman, James E.; Pincet, Frédéric

doi:10.1073/pnas.1307685110

Cited by 150 publications

(179 citation statements)

References 32 publications

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“…In addition, ADP-ribosylation factor 1 (Arf1)/COPI complex has been found to have a key role in the triggering the formation of membrane bridges linking the ER and LDs [28,29]. However, freeze-fracture electron microscopy showed adjacent LDs and ER with independent membranes [30], and ER proteins such as GPAT4 are only observed in a subset of LDs, indicating that such connections could be transient or not present in some LDs.…”

Section: The Er In Ld Biogenesis and Growthmentioning

confidence: 99%

Lipid droplet growth: regulation of a dynamic organelle

Barneda

Christian

2017

Current Opinion in Cell Biology

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Intracellular lipid droplets (LDs) are remarkably dynamic and complex organelles that enact regulated storage and release of lipids to fulfil their fundamental roles in energy metabolism, membrane synthesis and provision of lipid-derived signaling molecules.Although small LDs are observed in all types of eukaryotic cells, it is adipocytes that present the widest range of sizes up to the massive unilocular droplet of a white adipocyte. Our knowledge of the proteins and associated processes that control LD dynamics is improving. The dynamic expression of LD-associated proteins is vital for controlling LD biology and is most apparent during adipocyte differentiation. Recent findings on the molecular mechanisms of lipid droplet enlargement reveal the importance of distinct functional groups of proteins and phospholipids.Highlights (max 5 points 85 characters each) Lipid droplet fusion involves major changes in the LD membrane components.Phosphatidic Acid is a key regulator of LD dynamics.Adipocyte differentiation invokes profound regulation of lipid droplet proteins.Transitions between white and BRITE adipocytes require lipid droplet remodelling.

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Section: The Er In Ld Biogenesis and Growthmentioning

confidence: 99%

Lipid droplet growth: regulation of a dynamic organelle

Barneda

Christian

2017

Current Opinion in Cell Biology

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“…GBF1 itself is recruited to lipid droplets through its 'homology downstream of Sec7' (HDS)1 domain, which binds to lipid droplets in cells and in vitro (Bouvet et al, 2013). Arf1-GTP and COPI can function directly on the lipid droplet surface and have been shown to mediate the budding of 60-100-nm diameter droplets from an artificial droplet surface in vitro (Thiam et al, 2013). This mechanism is important for the regulation of the surface properties of lipid droplets during different stages of their metabolism in cells (Wilfling et al, 2014).…”

Section: Arf1 In Lipid Droplet Functionmentioning

confidence: 99%

Arfs at a Glance

Jackson

Bouvet

2014

Journal of Cell Science

119

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 both yeast and neurons, α-syn associates with lipid rafts, suggesting that α-syn displays similar lipid-binding preferences in both cell types. The exact composition of α-syn's preferred lipid environment is not understood; however, current work suggests that α-syn is sensitive both to the type of lipids and how they are packed into the bilayer (12,13).…”

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confidence: 99%

Splice isoform and pharmacological studies reveal that sterol depletion relocalizes α-synuclein and enhances its toxicity

Valastyan¹,

Termine²,

Lindquist³

2014

Proc. Natl. Acad. Sci. U.S.A.

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Synucleinopathies are neurodegenerative diseases associated with toxicity of the lipid-binding protein α-synuclein (α-syn). When expressed in yeast, α-syn associates with membranes at the endoplasmic reticulum and traffics with vesicles out to the plasma membrane. At higher levels it elicits a number of phenotypes, including blocking vesicle trafficking. The expression of α-syn splice isoforms varies with disease, but how these isoforms affect protein function is unknown. We investigated two of the most abundant isoforms, resulting in deletion of exon four (α-synΔ4) or exon six (α-synΔ6). α-SynΔ4, missing part of the lipid-binding domain, had reduced toxicity and membrane binding. α-SynΔ6, missing part of the protein-protein interaction domain, had reduced toxicity but no reduction in membrane binding. To compare the mechanism by which the splice isoforms exert toxicity, equally toxic strains were probed with genetic modifiers of α-syn-induced toxicity. Most modifiers equally altered the toxicity induced by the splice isoforms and full-length α-syn (α-synFL). However, the splice isoform strains responded differently to a sterol-binding protein, leading us to examine the effect of sterols on α-syn-induced toxicity. Upon inhibition of sterol synthesis, α-synFL and α-synΔ6, but not α-synΔ4, showed decreased plasma membrane association, increased vesicular association, and increased cellular toxicity. Thus, higher membrane sterol concentrations favor plasma membrane binding of α-synFL and α-synΔ6 and may be protective of synucleinopathy progression. Given the common use of cholesterol-reducing statins and these potential effects on membrane binding proteins, further investigation of how sterol concentration and α-syn splice isoforms affect vesicular trafficking in synucleinopathies is warranted.

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COPI buds 60-nm lipid droplets from reconstituted water–phospholipid–triacylglyceride interfaces, suggesting a tension clamp function

Cited by 150 publications

References 32 publications

Lipid droplet growth: regulation of a dynamic organelle

Lipid droplet growth: regulation of a dynamic organelle

Arfs at a Glance

Splice isoform and pharmacological studies reveal that sterol depletion relocalizes α-synuclein and enhances its toxicity

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