scholarly journals Criticality of plasma membrane lipids reflects activation state of macrophage cells

2019 ◽  
Author(s):  
Eugenia Cammarota ◽  
Chiara Soriani ◽  
Raphaelle Taub ◽  
Fiona Morgan ◽  
Jiro Sakai ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Critical Point ◽  
Membrane Lipids ◽  
Membrane Lipid ◽  
Membrane Receptors ◽  
Critical Conditions ◽  
Membrane Composition ◽  
Macrophage Cells ◽  
Lipid Species ◽  
Anti Inflammatory

AbstractSignalling is of particular importance in immune cells, and upstream in the signalling pathway many membrane receptors are functional only as complexes, co-locating with particular lipid species. Work over the last 15 years has shown that plasma membrane lipid composition is close to a critical point of phase separation, with evidence that cells adapt their composition in ways that alter the proximity to this thermodynamical point. Macrophage cells are a key component of the innate immune system, responsive to infections, regulating the local state of inflammation. We investigate changes in the plasma membrane’s proximity to the critical point, as a response to stimulation by various pro- and anti-inflammatory agents. Pro-inflammatory (IFN-γ, Kdo-LipidA, LPS) perturbations induce an increase in the transition temperature of the GMPVs; anti-inflammatory IL4 has the opposite effect. These changes recapitulate complex plasma membrane composition changes, and are consistent with lipid criticality playing a master regulatory role: being closer to critical conditions increases membrane protein activity.

scholarly journals Criticality of plasma membrane lipids reflects activation state of macrophage cells

2020 ◽  
Vol 17 (163) ◽  
pp. 20190803 ◽  
Author(s):  
Eugenia Cammarota ◽  
Chiara Soriani ◽  
Raphaelle Taub ◽  
Fiona Morgan ◽  
Jiro Sakai ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Critical Point ◽  
Membrane Lipids ◽  
Membrane Receptors ◽  
Interleukin 4 ◽  
Critical Conditions ◽  
Membrane Composition ◽  
Macrophage Cells ◽  
Lipid Species ◽  
Anti Inflammatory

Signalling is of particular importance in immune cells, and upstream in the signalling pathway many membrane receptors are functional only as complexes, co-locating with particular lipid species. Work over the last 15 years has shown that plasma membrane lipid composition is close to a critical point of phase separation, with evidence that cells adapt their composition in ways that alter the proximity to this thermodynamic point. Macrophage cells are a key component of the innate immune system, are responsive to infections and regulate the local state of inflammation. We investigate changes in the plasma membrane’s proximity to the critical point as a response to stimulation by various pro- and anti-inflammatory agents. Pro-inflammatory (interferon γ , Kdo 2-Lipid A, lipopolysaccharide) perturbations induce an increase in the transition temperature of giant plasma membrane vesicles; anti-inflammatory interleukin 4 has the opposite effect. These changes recapitulate complex plasma membrane composition changes, and are consistent with lipid criticality playing a master regulatory role: being closer to critical conditions increases membrane protein activity.

scholarly journals Exofacial membrane composition and lipid metabolism regulates plasma membrane P4-ATPase substrate specificity

2020 ◽  
Author(s):  
Bartholomew P. Roland ◽  
Bhawik K. Jain ◽  
Todd R. Graham
Keyword(s):  
Plasma Membrane ◽  
Membrane Lipids ◽  
Asymmetric Distribution ◽  
Membrane Composition ◽  
Membrane Biology ◽  
Membrane Asymmetry ◽  
Type Iv ◽  
Lipid Species ◽  
Endogenous Lipid ◽  
A Cell

AbstractThe plasma membrane of a cell is characterized by an asymmetric distribution of lipid species across the exofacial and cytofacial aspects of the bilayer. The regulation of membrane asymmetry is a fundamental characteristic of membrane biology, and is crucial for signal transduction, vesicle transport, and cell division. The type-IV family of P-ATPases, or P4-ATPases, establish membrane asymmetry by selection and transfer of a subset of membrane lipids from the lumenal or exofacial leaflet to the cytofacial aspect of the bilayer. It is still unclear how these enzymes sort through the spectrum of lipids within the membrane to identify their desired substrate(s) and how the membrane environment modulates this activity. Therefore, we tested how the yeast plasma membrane P4-ATPase, Dnf2, responds to changes in membrane composition induced by perturbation of endogenous lipid biosynthetic pathways or exogenous application of lipid. The primary substrates of Dnf2 are two chemically divergent lipids, glucosylceramide (GlcCer) and phosphatidylcholine ((PC) or their lyso-lipid derivatives), and we find that these substrates compete with each other for transport. Acutely inhibiting sphingolipid synthesis using myriocin attenuates transport of exogenously applied GlcCer without perturbing PC transport. Deletion of genes controlling later steps of glycosphingolipid production also perturb GlcCer transport to a greater extent than PC transport. Surprisingly, application of lipids that are poor transport substrates differentially affect PC and GlcCer transport by Dnf2, thus altering substrate preference. Our data indicate that Dnf2 exhibits exquisite sensitivity to the membrane composition; thus, providing feedback onto the function of the P4-ATPases.

scholarly journals Defining how multiple lipid species interact with inward rectifier potassium (Kir2) channels

2020 ◽  
Vol 117 (14) ◽  
pp. 7803-7813 ◽  
Author(s):  
Anna L. Duncan ◽  
Robin A. Corey ◽  
Mark S. P. Sansom
Keyword(s):  
Plasma Membrane ◽  
Membrane Lipids ◽  
Membrane Lipid ◽  
Inward Rectifier ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Anionic Lipid ◽  
Lipid Interactions ◽  
Interaction Sites ◽  
Lipid Species

Protein–lipid interactions are a key element of the function of many integral membrane proteins. These potential interactions should be considered alongside the complexity and diversity of membrane lipid composition. Inward rectifier potassium channel (Kir) Kir2.2 has multiple interactions with plasma membrane lipids: Phosphatidylinositol (4, 5)-bisphosphate (PIP2) activates the channel; a secondary anionic lipid site has been identified, which augments the activation by PIP2; and cholesterol inhibits the channel. Molecular dynamics simulations are used to characterize in molecular detail the protein–lipid interactions of Kir2.2 in a model of the complex plasma membrane. Kir2.2 has been simulated with multiple, functionally important lipid species. From our simulations we show that PIP2interacts most tightly at the crystallographic interaction sites, outcompeting other lipid species at this site. Phosphatidylserine (PS) interacts at the previously identified secondary anionic lipid interaction site, in a PIP2concentration-dependent manner. There is interplay between these anionic lipids: PS interactions are diminished when PIP2is not present in the membrane, underlining the need to consider multiple lipid species when investigating protein–lipid interactions.

scholarly journals Exofacial membrane composition and lipid metabolism regulates plasma membrane P4-ATPase substrate specificity

2020 ◽  
Vol 295 (52) ◽  
pp. 17997-18009 ◽  
Author(s):  
Bhawik Kumar Jain ◽  
Bartholomew P. Roland ◽  
Todd R. Graham
Keyword(s):  
Plasma Membrane ◽  
Membrane Lipids ◽  
Ergosterol Biosynthesis ◽  
Asymmetric Distribution ◽  
Membrane Composition ◽  
Membrane Biology ◽  
Membrane Asymmetry ◽  
Type Iv ◽  
Lipid Species ◽  
A Cell

The plasma membrane of a cell is characterized by an asymmetric distribution of lipid species across the exofacial and cytofacial aspects of the bilayer. Regulation of membrane asymmetry is a fundamental characteristic of membrane biology and is crucial for signal transduction, vesicle transport, and cell division. The type IV family of P-ATPases, or P4-ATPases, establishes membrane asymmetry by selection and transfer of a subset of membrane lipids from the lumenal or exofacial leaflet to the cytofacial aspect of the bilayer. It is unclear how P4-ATPases sort through the spectrum of membrane lipids to identify their desired substrate(s) and how the membrane environment modulates this activity. Therefore, we tested how the yeast plasma membrane P4-ATPase, Dnf2, responds to changes in membrane composition induced by perturbation of endogenous lipid biosynthetic pathways or exogenous application of lipid. The primary substrates of Dnf2 are glucosylceramide (GlcCer) and phosphatidylcholine (PC, or their lyso-lipid derivatives), and we find that these substrates compete with each other for transport. Acutely inhibiting sphingolipid synthesis using myriocin attenuates transport of exogenously applied GlcCer without perturbing PC transport. Deletion of genes controlling later steps of glycosphingolipid production also perturb GlcCer transport to a greater extent than PC transport. In contrast, perturbation of ergosterol biosynthesis reduces PC and GlcCer transport equivalently. Surprisingly, application of lipids that are poor transport substrates differentially affects PC and GlcCer transport by Dnf2, thus altering substrate preference. Our data indicate that Dnf2 exhibits exquisite sensitivity to the membrane composition, thus providing feedback onto the function of the P4-ATPases.

scholarly journals Lipid Remodeling Confers Osmotic Stress Tolerance to Embryogenic Cells during Cryopreservation

2021 ◽  
Vol 22 (4) ◽  
pp. 2174
Author(s):  
Liang Lin ◽  
Junchao Ma ◽  
Qin Ai ◽  
Hugh W. Pritchard ◽  
Weiqi Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Technology Development ◽  
Membrane Lipids ◽  
Species Conservation ◽  
Membrane Lipid ◽  
Cell Integrity ◽  
Embryogenic Cells ◽  
Osmotic Stress Tolerance ◽  
Lipid Species ◽  
Magnolia Officinalis

Plant species conservation through cryopreservation using plant vitrification solutions (PVS) is based in empiricism and the mechanisms that confer cell integrity are not well understood. Using ESI-MS/MS analysis and quantification, we generated 12 comparative lipidomics datasets for membranes of embryogenic cells (ECs) of Magnolia officinalis during cryogenic treatments. Each step of the complex PVS-based cryoprotocol had a profoundly different impact on membrane lipid composition. Loading treatment (osmoprotection) remodeled the cell membrane by lipid turnover, between increased phosphatidic acid (PA) and phosphatidylglycerol (PG) and decreased phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The PA increase likely serves as an intermediate for adjustments in lipid metabolism to desiccation stress. Following PVS treatment, lipid levels increased, including PC and PE, and this effectively counteracted the potential for massive loss of lipid species when cryopreservation was implemented in the absence of cryoprotection. The present detailed cryobiotechnology findings suggest that the remodeling of membrane lipids and attenuation of lipid degradation are critical for the successful use of PVS. As lipid metabolism and composition varies with species, these new insights provide a framework for technology development for the preservation of other species at increasing risk of extinction.

scholarly journals Impact of Membrane Lipids on UapA and AzgA Transporter Subcellular Localization and Activity in Aspergillus nidulans

2021 ◽  
Vol 7 (7) ◽  
pp. 514
Author(s):  
Mariangela Dionysopoulou ◽  
George Diallinas
Keyword(s):  
Plasma Membrane ◽  
Subcellular Localization ◽  
Aspergillus Nidulans ◽  
Membrane Lipids ◽  
Membrane Lipid ◽  
Lipid Biosynthesis ◽  
Transport Kinetics ◽  
Negative Effect ◽  
And Function

Recent biochemical and biophysical evidence have established that membrane lipids, namely phospholipids, sphingolipids and sterols, are critical for the function of eukaryotic plasma membrane transporters. Here, we study the effect of selected membrane lipid biosynthesis mutations and of the ergosterol-related antifungal itraconazole on the subcellular localization, stability and transport kinetics of two well-studied purine transporters, UapA and AzgA, in Aspergillus nidulans. We show that genetic reduction in biosynthesis of ergosterol, sphingolipids or phosphoinositides arrest A. nidulans growth after germling formation, but solely blocks in early steps of ergosterol (Erg11) or sphingolipid (BasA) synthesis have a negative effect on plasma membrane (PM) localization and stability of transporters before growth arrest. Surprisingly, the fraction of UapA or AzgA that reaches the PM in lipid biosynthesis mutants is shown to conserve normal apparent transport kinetics. We further show that turnover of UapA, which is the transporter mostly sensitive to membrane lipid content modification, occurs during its trafficking and by enhanced endocytosis, and is partly dependent on autophagy and Hect-type HulARsp5 ubiquitination. Our results point out that the role of specific membrane lipids on transporter biogenesis and function in vivo is complex, combinatorial and transporter-dependent.

scholarly journals Monoclonal antibodies as probes of epithelial membrane polarization.

1985 ◽  
Vol 101 (6) ◽  
pp. 2173-2180 ◽  
Author(s):  
R J Turner ◽  
J Thompson ◽  
S Sariban-Sohraby ◽  
J S Handler
Keyword(s):  
Monoclonal Antibodies ◽  
Plasma Membrane ◽  
Membrane Lipids ◽  
Apical Plasma Membrane ◽  
Epithelial Cell Line ◽  
Lipid Species ◽  
Antigen Complex ◽  
Kidney Epithelial Cell ◽  
Kidney Epithelial Cell Line ◽  
Lipid Antigen

Monoclonal antibodies directed against antigens in the apical plasma membrane of the toad kidney epithelial cell line A6 were produced to probe the phenomena that underlie the genesis and maintenance of epithelial polarity. Two of these antibodies, 17D7 and 18C3, were selected for detailed study here. 17D7 is directed against a 23-kD peptide found on both the apical and basolateral surfaces of the A6 epithelium whereas 18C3 recognizes a lipid localized to the apical membrane only. This novel observation of an apically localized epithelial lipid species indicates the existence of a specific sorting and insertion process for this, and perhaps other, epithelial plasma membrane lipids. The antibody-antigen complexes formed by both these monoclonal antibodies are rapidly internalized by the A6 cells, but only the 18C3-antigen complex is recycled to the plasma membrane. In contrast to the apical localization of the free antigen, however, the 18C3-antigen complex is recycled to both the apical and basolateral surface of the epithelium, which indicates that monoclonal antibody binding interferes in some way with the normal sorting process for this apical lipid antigen.

scholarly journals Comparison of Erythrocyte Membrane Lipid Profiles between NAFLD Patients with or without Hyperlipidemia

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Wenbin Chen ◽  
Shanshan Shao ◽  
Hu Cai ◽  
Jie Han ◽  
Tian Guo ◽  
...  
Keyword(s):  
Erythrocyte Membrane ◽  
Cell Function ◽  
Membrane Lipids ◽  
Weight Percent ◽  
Membrane Lipid ◽  
Lipid Profiles ◽  
Data Sets ◽  
Lipid Profiling ◽  
Nonalcoholic Fatty Liver ◽  
Lipid Species

Objectives. Nonalcoholic fatty liver disease (NAFLD) and hyperlipidemia (HL) are common metabolic disorders due to overnutrition and obesity. NAFLD is often associated with hyperlipidemia. The aim of this study was to identify and compare the erythrocyte membrane lipids profile in NAFLD patients with or without HL. Methods. A total of 112 subjects (with similar age and body mass index) were divided into four groups: (1) normal controls, (2) NAFLD alone, (3) HL alone, and (4) NAFLD combined with HL (NAFLD + HL). Lipid was extracted from the erythrocyte membrane, and lipid profiles of subjects were analyzed by liquid chromatography mass spectrometry (LC-MS). Results. Data sets from 103 subjects were adopted for lipidomic analysis. Significant changes of lipid species were observed in patient groups, especially in the HL group and NAFLD + HL group. The HL group showed increased level of most lipid species, and decreased level of most lipid species was observed in the NAFLD + HL group. The weight percent of myristic acid, stearic acid, erucic acid, and docosahexaenoic acid also showed distinct variation between different groups. Conclusions. NAFLD, HL, and NAFLD + HL all had an impact on lipid profiling of the erythrocyte membrane. The influence of NAFLD alone is less important compared with HL. Some lipids should be highlighted because of their specific role in cell function and systemic metabolism.

scholarly journals Plasma Membrane Lipid Domains as Platforms for Vesicle Biogenesis and Shedding?

Biomolecules ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 94 ◽  
Author(s):  
Hélène Pollet ◽  
Louise Conrard ◽  
Anne-Sophie Cloos ◽  
Donatienne Tyteca
Keyword(s):  
Plasma Membrane ◽  
Membrane Lipids ◽  
Disease Diagnosis ◽  
Membrane Lipid ◽  
Lipid Domains ◽  
Disease Evolution ◽  
Physiological Processes ◽  
Plasma Membrane Lipid ◽  
Vesicle Biogenesis ◽  
Few Data

Extracellular vesicles (EVs) contribute to several pathophysiological processes and appear as emerging targets for disease diagnosis and therapy. However, successful translation from bench to bedside requires deeper understanding of EVs, in particular their diversity, composition, biogenesis and shedding mechanisms. In this review, we focus on plasma membrane-derived microvesicles (MVs), far less appreciated than exosomes. We integrate documented mechanisms involved in MV biogenesis and shedding, focusing on the red blood cell as a model. We then provide a perspective for the relevance of plasma membrane lipid composition and biophysical properties in microvesiculation on red blood cells but also platelets, immune and nervous cells as well as tumor cells. Although only a few data are available in this respect, most of them appear to converge to the idea that modulation of plasma membrane lipid content, transversal asymmetry and lateral heterogeneity in lipid domains may play a significant role in the vesiculation process. We suggest that lipid domains may represent platforms for inclusion/exclusion of membrane lipids and proteins into MVs and that MVs could originate from distinct domains during physiological processes and disease evolution.

scholarly journals Ion channels can be allosterically regulated by membrane domains near a de-mixing critical point

2018 ◽  
Vol 150 (12) ◽  
pp. 1769-1777 ◽  
Author(s):  
Ofer Kimchi ◽  
Sarah L. Veatch ◽  
Benjamin B. Machta
Keyword(s):  
Plasma Membrane ◽  
Ion Channels ◽  
Ising Model ◽  
Critical Point ◽  
Membrane Vesicles ◽  
Membrane Properties ◽  
Membrane Composition ◽  
Plasma Membrane Vesicles ◽  
Liquid Phases ◽  
Markovian Dynamics

Ion channels are embedded in the plasma membrane, a compositionally diverse two-dimensional liquid that has the potential to exert profound influence on their function. Recent experiments suggest that this membrane is poised close to an Ising critical point, below which cell-derived plasma membrane vesicles phase separate into coexisting liquid phases. Related critical points have long been the focus of study in simplified physical systems, but their potential roles in biological function have been underexplored. Here we apply both exact and stochastic techniques to the lattice Ising model to study several ramifications of proximity to criticality for idealized lattice channels, whose function is coupled through boundary interactions to critical fluctuations of membrane composition. Because of diverging susceptibilities of system properties to thermodynamic parameters near a critical point, such a lattice channel’s activity becomes strongly influenced by perturbations that affect the critical temperature of the underlying Ising model. In addition, its kinetics acquire a range of time scales from its surrounding membrane, naturally leading to non-Markovian dynamics. Our model may help to unify existing experimental results relating the effects of small-molecule perturbations on membrane properties and ion channel function. We also suggest ways in which the role of this mechanism in regulating real ion channels and other membrane-bound proteins could be tested in the future.

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