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 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 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 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 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 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.

scholarly journals Expression of plasma membrane receptor genes during megakaryocyte development

2013 ◽  
Vol 45 (6) ◽  
pp. 217-227 ◽  
Author(s):  
Sijie Sun ◽  
Wenjing Wang ◽  
Yvette Latchman ◽  
Dayong Gao ◽  
Bruce Aronow ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Platelet Function ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Membrane Receptors ◽  
Interleukin 4 ◽  
Environmental Cues ◽  
A Genome ◽  
Plasma Membrane Receptor ◽  
Plasma Membrane Receptors

Megakaryocyte (MK) development is critically informed by plasma membrane-localized receptors that integrate a multiplicity of environmental cues. Given that the current understanding about receptors and ligands involved in megakaryocytopoiesis is based on single targets, we performed a genome-wide search to identify a plasma membrane receptome for developing MKs. We identified 40 transmembrane receptor genes as being upregulated during MK development. Seven of the 40 receptor-associated genes were selected to validate the dataset. These genes included: interleukin-9 receptor (IL9R), transforming growth factor, β receptor II (TGFBR2), interleukin-4 receptor (IL4R), colony stimulating factor-2 receptor-beta (CSFR2B), adiponectin receptor (ADIPOR2), thrombin receptor (F2R), and interleukin-21 receptor (IL21R). RNA and protein analyses confirmed their expression in primary human MKs. Matched ligands to IL9R, TGFBR2, IL4R, CSFR2B, and ADIPOR2 affected megakaryocytopoiesis. IL9 was unique in its ability to increase the number of MKs formed. In contrast, MK colony formation was inhibited by adiponectin, TGF-β, IL4, and GM-CSF. The thrombin-F2R axis affected platelet function, but not MK development, while IL21 had no apparent detectable effects. ADP-induced platelet aggregation was suppressed by IL9, TGF-β, IL4, and adiponectin. Overall, six of seven of the plasma membrane receptors were confirmed to have functional roles in MK and platelet biology. Also, results show for the first time that adiponectin plays a regulatory role in MK development. Together these data support a strong likelihood that the 40 transmembrane genes identified as being upregulated during MK development will be an important resource to the research community for deciphering the complex repertoire of environmental cues regulating megakaryocytopoiesis and/or platelet function.

The influence of cold acclimation on the lipid composition and cryobehaviour of the plasma membrane of isolated rye protoplasts

1990 ◽  
Vol 326 (1237) ◽  
pp. 571-583 ◽  
Keyword(s):  
Plasma Membrane ◽  
Phase Transitions ◽  
Cold Acclimation ◽  
Lipid Composition ◽  
Membrane Lipids ◽  
Freezing Injury ◽  
Lipid Species ◽  
Differential Behaviour ◽  
Cell Dehydration ◽  
Osmotic Contraction

Destabilization of the plasma membrane, which is a primary cause of freezing injury, is a consequence of freeze-induced osmotic stresses and cell dehydration. However, the mechanism of injury depends on the magnitude of the osmotic stress and the extent of cell dehydration. Over the range of 0 to — 5 °C, destabilization of the plasma membrane in protoplasts isolated from non-acclimated rye leaves is a result of osmotic excursions, because freeze-induced osmotic contraction results in endocytotic vesiculation of the plasma membrane and sufficiently large area reductions are irreversible. At lower temperatures, the protoplasts are subjected to extremely large osmotic pressures ( — 12 MPa at —10 °C), and there are several changes in the ultrastructure of the plasma membrane, including the formation of aparticulate domains and lamellar- to hexagonaln-phase transitions. These changes, which are manifestations of demixing of the membrane components, are predicted by a theory of bilayer interactions at low levels of hydration. During cold acclimation, the cryobehaviour of the plasma membrane is altered; osmotic contraction results in the reversible formation of exocytotic extrusions and the propensity for dehydration-induced demixing and lamellar- to hexagonaln-phase transitions is decreased. In both cases, the differential behaviour is also observed in liposomes prepared from plasma membrane lipids isolated from non-acclimated and cold-acclimated leaves. However, as no lipid species are unique to the plasma membrane of either non-acclimated or cold-acclimated leaves, the differential behaviour is caused by altered lipid-lipid interactions because of different proportions of the lipid species. Hence the behaviour of the plasma membrane can be altered by using a protoplast-liposome fusion procedure to selectively modify the lipid composition of the plasma membrane. These studies provide direct evidence that the increased cryostability of the plasma membrane is a consequence of alterations in its lipid composition.

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.

55 Sow Milk Lipidome Study Reveals Changes in Fatty Acyl Residues in Triglycerides and Phosphatidylglycerol, but Not in Plasma Membrane Phospholipids Across Lactation

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 152-153
Author(s):  
Sarah Luecke ◽  
Aridany Suarez-Trujillo ◽  
Lea Logan ◽  
Kara R Stewart ◽  
Christina Ferreira ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Milk Fat ◽  
Membrane Lipids ◽  
Multiple Reaction Monitoring ◽  
Late Pregnancy ◽  
Fatty Acyl ◽  
Variable Component ◽  
Membrane Phospholipids ◽  
Mature Milk ◽  
Lipid Species

Abstract Sow milk fat content is crucial to neonatal survival, as it is utilized for thermogenesis and nutrition. However, fat is the most variable component of milk in concentration and lipid species. Characterizing lipid changes across the course of a sow’s lactation may help identify molecules or systems to target to help enhance milk fat quality and quantity for neonatal survival and growth. Percent fat variation is greatest in colostrum, the first milk. Little is known regarding colostrum synthesis, other than it accumulates in the gland beginning in mid-late pregnancy, which is prior to the initiation of fatty acid synthesis in lactocytes. The objective of this study was to characterize changes in lipid composition of milk across the course of lactation and determine if there was a relationship between fat percent and lipid species in colostrum and mature milk. Milk was collected from 9 multiparous sows on days 0, 3, 7, and 14 relative to birth. Percent fat was determined by creamatocrit, and found to be different (p< 0.05) between day 0 (12.36 ± 5.90%) and day 3 (16.22 ± 3.65%) but not between day 7 (13.13 ± 2.19%) and 14 (12.13 ± 2.45%). Fat was extracted from milk using the Bligh-Dyer method and profiled using multiple reaction monitoring. Amounts of lipid species were calculated relative to standards and data analysis was performed using Metaboanalyst 4.0. Principle component analysis revealed lactation day had a significant effect on distribution of fats. Triacylglycerides (TAG), phosphatidylglycerol (PG), and plasma membrane lipids were modified from colostrum to mature milk, with a significant increase in PGs and TAGs across the course of lactation. Correlation analysis of percent fat with lipid concentration indicated strong relationships (P < 0.05; |r| >0.80) with eight lipids. No differences are found in the abundance of plasma membrane phospholipids, sphingomyelin, or cholesterol esters across lactation days.

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