Curvature, Lipid Packing, and Electrostatics of Membrane Organelles: Defining Cellular Territories in Determining Specificity

Bigay, Joëlle; Antonny, Bruno

doi:10.1016/j.devcel.2012.10.009

Cited by 456 publications

(523 citation statements)

References 102 publications

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“…Both lipid composition and curvature concur to modulate the number and size of lipid-packing defects in model membranes. However, in a cellular context, it is their combination that gives rise to the unique interfacial properties of membranes 4 .…”

Section: Resultsmentioning

confidence: 99%

“…In addition, it is well established that lipid composition is a key parameter to tune the partitioning of proteins and peptides to lipid bilayers 2,4 . However, these two parameters are often conceptually separated when interpreting in vitro experiments even though they combine in cellular contexts.…”

Section: Discussionmentioning

confidence: 99%

“…As a result of these differences, transmembrane proteins travelling along the ER-Golgi-PM route and peripheral proteins transiently associating with these organelles experience different lipid environments [3][4][5] . For example, membrane electrostatics provided by negatively charged lipids directs the attachment of many proteins underneath the PM.…”

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confidence: 99%

“…In turn, this stress triggers a response characterized by the upregulation of a fatty acid desaturase (Ole1 in yeast) and the arrest of cholesterol synthesis [9][10][11][12] . In addition, several peripheral proteins involved in various functions (lipid transfer, autophagy, nuclear pore formation, vesicle tethering and protein coat dynamics) seem to recognize lipid-packing defects by adsorbing preferentially to positively curved membranes through the insertion of long amphipathic sequences 4,[13][14][15][16][17] .…”

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confidence: 99%

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A sub-nanometre view of how membrane curvature and composition modulate lipid packing and protein recruitment

et al. 2014

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Two parameters of biological membranes, curvature and lipid composition, direct the recruitment of many peripheral proteins to cellular organelles. Although these traits are often studied independently, it is their combination that generates the unique interfacial properties of cellular membranes. Here, we use a combination of in vivo, in vitro and in silico approaches to provide a comprehensive map of how these parameters modulate membrane adhesive properties. The correlation between the membrane partitioning of model amphipathic helices and the distribution of lipid-packing defects in membranes of different shape and composition explains how macroscopic membrane properties modulate protein recruitment by changing the molecular topography of the membrane interfacial region. Furthermore, our results suggest that the range of conditions that can be obtained in a cellular context is remarkably large because lipid composition and curvature have, under most circumstances, cumulative effects.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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A sub-nanometre view of how membrane curvature and composition modulate lipid packing and protein recruitment

et al. 2014

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“…First, the negatively charged PtdIns(4)P is concentrated in the later Golgi because of the constant cycling of the PtdIns(4)P phosphatase Sac1 between the cis-Golgi and ER (33,34). Second, phosphatidylserine, another major negatively charged phospholipid, is located mostly in the inner leaflet of the ER and cis-Golgi membranes but in the outer leaflet of compartment membranes later in the secretory pathway (35). Interestingly the β'-COP (30) and α-COP (31) juxtamembrane surfaces are similarly highly electronegative and thus also could contribute to selective membrane recruitment of coatomer.…”

Section: Discussionmentioning

confidence: 99%

Structural basis for the binding of tryptophan-based motifs by δ-COP

Suckling

Poon

Travis

et al. 2015

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

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Coatomer consists of two subcomplexes: the membrane-targeting, ADP ribosylation factor 1 (Arf1):GTP-binding βγδζ-COP F-subcomplex, which is related to the adaptor protein (AP) clathrin adaptors, and the cargo-binding αβ'e-COP B-subcomplex. We present the structure of the C-terminal μ-homology domain of the yeast δ-COP subunit in complex with the WxW motif from its binding partner, the endoplasmic reticulum-localized Dsl1 tether. The motif binds at a site distinct from that used by the homologous AP μ subunits to bind YxxΦ cargo motifs with its two tryptophan residues sitting in compatible pockets. We also show that the Saccharomyces cerevisiae Arf GTPase-activating protein (GAP) homolog Gcs1p uses a related WxxF motif at its extreme C terminus to bind to δ-COP at the same site in the same way. Mutations designed on the basis of the structure in conjunction with isothermal titration calorimetry confirm the mode of binding and show that mammalian δ-COP binds related tryptophan-based motifs such as that from ArfGAP1 in a similar manner. We conclude that δ-COP subunits bind Wx n(1-6) [WF] motifs within unstructured regions of proteins that influence the lifecycle of COPI-coated vesicles; this conclusion is supported by the observation that, in the context of a sensitizing domain deletion in Dsl1p, mutating the tryptophan-based motif-binding site in yeast causes defects in both growth and carboxypeptidase Y trafficking/processing. C OPI vesicles mediate retrograde trafficking from the Golgi to the endoplasmic reticulum (ER) and within the Golgi (reviewed in refs. 1-3). The COPI vesicle coat consists of two major components, coatomer and the small GTPase ADP ribosylation factor 1 (Arf1). Coatomer is an ∼600 kDa heteroheptameric complex consisting of two linked subcomplexes, the βγδζ-COP F-subcomplex and the αβ'e-COP B-subcomplex, all conserved from yeast to humans.Recent studies have led to a model for COPI-coated vesicle formation in which the F-subcomplex functions as a traditional Arf1:GTP effector but with two membrane-attached Arf1:GTP molecules binding to quasi-equivalent sites on a single F-subcomplex, recruiting F-subcomplex and its associated B-subcomplex onto the membrane en bloc (4). Once the vesicle has budded from its donor membrane, an Arf GTPase-activating protein (ArfGAP) catalyzes the hydrolysis of GTP on Arf1, and the Arf1:GDP dissociates from the membrane, followed later by the dissociation of the coatomer complex that was bound to the transport vesicle (5). ArfGAPs also have been proposed to function at different stages in vesicle biogenesis, both as terminators and, during an earlier cargoediting step, as effectors (reviewed in depth in ref. 6). In the final stages of its life, a COPI-coated vesicle docks with the ER via the Dsl1-tethering complex, completes uncoating, and finally undergoes SNARE-mediated fusion with the ER (7-9).The two main ArfGAPs associated with COPI-dependent retrograde transport in yeast are Gcs1p and Glo3p. These proteins can substitute for one another, at least partially,...

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Metabolism and functions of docosahexaenoic acid‐containing membrane glycerophospholipids

et al. 2017

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Omega‐3 (ω‐3) fatty acids (FAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are known to have important roles in human health and disease. Besides being utilized as fuel, ω‐3 FAs have specific functions based on their structural characteristics. These functions include serving as ligands for several receptors, precursors of lipid mediators, and components of membrane glycerophospholipids (GPLs). Since ω‐3 FAs (especially DHA) are highly flexible, the levels of DHA in GPLs may affect membrane biophysical properties such as fluidity, flexibility, and thickness. Here, we summarize some of the cellular mechanisms for incorporating DHA into membrane GPLs and propose biological effects and functions of DHA‐containing membranes of several cell and tissue types.

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Curvature, Lipid Packing, and Electrostatics of Membrane Organelles: Defining Cellular Territories in Determining Specificity

Cited by 456 publications

References 102 publications

A sub-nanometre view of how membrane curvature and composition modulate lipid packing and protein recruitment

A sub-nanometre view of how membrane curvature and composition modulate lipid packing and protein recruitment

Structural basis for the binding of tryptophan-based motifs by δ-COP

Metabolism and functions of docosahexaenoic acid‐containing membrane glycerophospholipids

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