A Cholesterol Recognition Motif in Human Phospholipid Scramblase 1

Posada, Itziar M. D.; Fantini, Jacques; Contreras, F.‐Xabier; Barrantes, Francisco J.; Alonso, Alicia; Goñi, Félix M.

doi:10.1016/j.bpj.2014.07.039

Cited by 23 publications

(16 citation statements)

References 56 publications

(69 reference statements)

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“…3C indicate that under these conditions, calcium induces structural changes in the membrane, transitioning to a gel-order phase, whereas at other concentrations the membrane hydration remains almost unchanged. A similar inhibitory effect of membrane state on Plscr1 activity has been observed when cholesterol levels increase in the plasma membrane [38].…”

Section: Phospholipid Scramblase 3 Is Involved In Calcium-dependent Psupporting

confidence: 68%

Topological characterization of the mitochondrial phospholipid scramblase 3

Luévano‐Martínez

Kowaltowski

2017

FEBS Letters

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Scramblases redistribute phospholipids in biological membranes. Phospholipid scramblase 3 (PLSCR3), which is located in mitochondria, has been reported to be involved in cardiolipin distribution from the inner to the outer membrane, thus regulating cellular processes such as apoptosis or mitophagy. However, the localization and topology of this protein has not been convincingly addressed to support a role in intermembrane phospholipid transfer. Here, we studied PLSCR3 topology within mitochondria. We show that PLSCR3 inserts in the inner membrane (IM) via its C-terminal transmembrane helix, whereas its N-terminal portion is oriented toward the intermembrane space where it is activated by calcium. Our results suggest that PLSCR3, via its C-terminal transmembrane domain, participates in the bidirectional movement of phospholipids within the IM.

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Section: Phospholipid Scramblase 3 Is Involved In Calcium-dependent Psupporting

confidence: 68%

Topological characterization of the mitochondrial phospholipid scramblase 3

Luévano‐Martínez

Kowaltowski

2017

FEBS Letters

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“…Sorting and activation of membrane proteins is the most studied function of lipid domains [54][55][56][57]. These effects can be attributed either to the modification of bilayer properties (thickness, curvature or surface tension) or to the binding of specific lipids to the protein surface.…”

Section: Lipid Domains As Modulators Of Piezo1 and Pmca Membrane Locamentioning

confidence: 99%

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

Conrard

Stommen

Cloos

et al. 2018

Cell Physiol Biochem

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Background/Aims: Red blood cells (RBC) have been shown to exhibit stable submicrometric lipid domains enriched in cholesterol (chol), sphingomyelin (SM), phosphatidylcholine (PC) or ganglioside GM1, which represent the four main lipid classes of their outer plasma membrane leaflet. However, whether those lipid domains co-exist at the RBC surface or are spatially related and whether and how they are subjected to reorganization upon RBC deformation are not known. Methods: Using fluorescence and/or confocal microscopy and well-validated probes, we compared these four lipid-enriched domains for their abundance, curvature association, lipid order, temperature dependence, spatial dissociation and sensitivity to RBC mechanical stimulation. Results: Our data suggest that three populations of lipid domains with decreasing abundance coexist at the RBC surface: (i) chol-enriched ones, associated with RBC high curvature areas; (ii) GM1/PC/chol-enriched ones, present in low curvature areas; and (iii) SM/PC/chol-enriched ones, also found in low curvature areas. Whereas chol-enriched domains gather in increased curvature areas upon RBC deformation, low curvature-associated lipid domains increase in abundance either upon calcium influx during RBC deformation (GM1/PC/chol-enriched domains) or upon secondary calcium efflux during RBC shape restoration (SM/PC/chol-enriched domains). Hence, abrogation of these two domain populations is accompanied by a strong impairment of the intracellular calcium balance. Conclusion: Lipid domains could contribute to calcium influx and efflux by controlling the membrane distribution and/or the activity of the mechano-activated ion channel Piezo1 and the calcium pump PMCA. Whether this results from lipid domain biophysical properties, the strength of their anchorage to the underlying cytoskeleton and/or their correspondence with inner plasma membrane leaflet lipids remains to be demonstrated.

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“…Cholesterol modulates the activity of a wide range of membrane receptors and ion channels in multiple ways, i.e., via general effects on the bulk bilayer lipid, altering membrane fluidity (el Battari, Ah-Kye, Muller, Sari, & Marvaldi, 1985;Lazar & Medzihradsky, 1992;Maguire & Druse, 1989) or curvature (Lee, 2004;Yesylevskyy, Demchenko, Kraszewski, & Ramseyer, 2013) or through direct binding to these proteins (Baier, Fantini, & Barrantes, 2011;Barrantes, 2004;Dopico & Bukiya, 2014;Fantini & Barrantes, 2013;Levitan, Singh, & Rosenhouse-Dantsker, 2014;Picazo-Juarez et al, 2011;Popot, Demel, Sobel, van Deenen, & Changeux, 1977;Posada et al, 2014;Singh, Shentu, Enkvetchakul, & Levitan, 2011;Rosenhouse-Dantsker, Noskov, Durdagi, Logothetis, & Levitan, 2013;Singh et al, 2012). The availability of the crystal structures of the β2-adrenergic receptor represented an important milestone in the identification of direct interactions between a paradigmatic transmembrane (TM) protein and member of the most abundant and functionally important superfamily of receptors in eukaryotic cells, i.e., the G-protein-coupled receptors (GPCRs) on the one hand and cholesterol (Cherezov et al, 2007;Rosenbaum et al, 2007) on the other.…”

Section: Introductionmentioning

confidence: 99%

Relevance of CARC and CRAC Cholesterol-Recognition Motifs in the Nicotinic Acetylcholine Receptor and Other Membrane-Bound Receptors

Scala

Baier

Evans

et al. 2017

Current Topics in Membranes

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Cholesterol is a ubiquitous neutral lipid, which finely tunes the activity of a wide range of membrane proteins, including neurotransmitter and hormone receptors and ion channels. Given the scarcity of available X-ray crystallographic structures and the even fewer in which cholesterol sites have been directly visualized, application of in silico computational methods remains a valid alternative for the detection and thermodynamic characterization of cholesterol-specific sites in functionally important membrane proteins. The membrane-embedded segments of the paradigm neurotransmitter receptor for acetylcholine display a series of cholesterol consensus domains (which we have coined "CARC"). The CARC motif exhibits a preference for the outer membrane leaflet and its mirror motif, CRAC, for the inner one. Some membrane proteins possess the double CARC-CRAC sequences within the same transmembrane domain. In addition to in silico molecular modeling, the affinity, concentration dependence, and specificity of the cholesterol-recognition motif-protein interaction have recently found experimental validation in other biophysical approaches like monolayer techniques and nuclear magnetic resonance spectroscopy. From the combined studies, it becomes apparent that the CARC motif is now more firmly established as a high-affinity cholesterol-binding domain for membrane-bound receptors and remarkably conserved along phylogenetic evolution.

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A Cholesterol Recognition Motif in Human Phospholipid Scramblase 1

Cited by 23 publications

References 56 publications

Topological characterization of the mitochondrial phospholipid scramblase 3

Topological characterization of the mitochondrial phospholipid scramblase 3

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

Relevance of CARC and CRAC Cholesterol-Recognition Motifs in the Nicotinic Acetylcholine Receptor and Other Membrane-Bound Receptors

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