Sub-resolution lipid domains exist in the plasma membrane and regulate protein diffusion and distribution

Owen, Dylan M.; Williamson, David J.; Magenau, Astrid; Gaus, Katharina

doi:10.1038/ncomms2273

Cited by 240 publications

(219 citation statements)

References 48 publications

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“…However, lipid domains may not be static entities but constantly reshaped in membranes that exhibit lipid phase separation (65). Indeed, it may be the ability to reorganize the plasma membrane upon TCR triggering, and not the basal membrane order and composition per se, that is functionally important for downstream activation.…”

Section: Discussionmentioning

confidence: 99%

Prolonged Intake of Dietary Lipids Alters Membrane Structure and T Cell Responses in LDLr−/− Mice

Pollock

Tedla

Hancock

et al. 2016

The Journal of Immunology

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Although it is recognized that lipids and membrane organization in T cells affect signaling and T cell activation, to what extent dietary lipids alter T cell responsiveness in the absence of obesity and inflammation is not known. In this study, we fed low-density lipoprotein receptor knockout mice a Western high-fat diet for 1 or 9 wk and examined T cell responses in vivo along with T cell lipid composition, membrane order, and activation ex vivo. Our data showed that high levels of circulating lipids for a prolonged period elevated CD4+ and CD8+ T cell proliferation and resulted in an increased proportion of CD4+ central-memory T cells within the draining lymph nodes following induction of contact hypersensitivity. In addition, the 9-wk Western high-fat diet elevated the total phospholipid content and monounsaturated fatty acid level, but decreased saturated phosphatidylcholine and sphingomyelin within the T cells. The altered lipid composition in the circulation, and of T cells, was also reflected by enhanced membrane order at the activation site of ex vivo activated T cells that corresponded to increased IL-2 mRNA levels. In conclusion, dietary lipids can modulate T cell lipid composition and responses in lipoprotein receptor knockout mice even in the absence of excess weight gain and a proinflammatory environment.

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Section: Discussionmentioning

confidence: 99%

Prolonged Intake of Dietary Lipids Alters Membrane Structure and T Cell Responses in LDLr−/− Mice

Pollock

Tedla

Hancock

et al. 2016

The Journal of Immunology

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“…Despite some controversy surrounding their existence (74), the presence of ordered (Lo) cholesterol-rich lipid domains in cell membranes has been strongly supported by several recent studies (75,76). Such microdomains may play essential roles in the spatial organization and localization of plasma membrane components.…”

Section: Discussionmentioning

confidence: 99%

The Mechanism of Membrane Disruption by Cytotoxic Amyloid Oligomers Formed by Prion Protein(106–126) Is Dependent on Bilayer Composition

Walsh

Vanderlee

Yau

et al. 2014

Journal of Biological Chemistry

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Background: Nonfibrillar amyloid oligomers are cytotoxic and may act through physical disruption of cell membranes. Results: Cytotoxic oligomers of the amyloid peptide PrP(106 -126) disrupt membranes through distinct mechanisms, depending on lipid composition. Conclusion: Cytotoxicity of PrP(106 -126) oligomers can occur through at least two different physical processes. Significance: Mechanisms for the membrane disruption of amyloid oligomers are proposed, providing new insight into their cytotoxicity.

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“…As a final way of experimentally validating our flicker approach, we investigated use of 7-ketocholesterol (7-KC), a probe that reduces lipid packing and lipid order by integrating into the RBC membrane (36). We found that 7-KC significantly and specifically reduces bending modulus without affecting tension properties (Fig.…”

Section: Eba175mentioning

confidence: 99%

Plasmodium falciparum erythrocyte-binding antigen 175 triggers a biophysical change in the red blood cell that facilitates invasion

Koch

Wright

Otto

et al. 2017

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

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Invasion of the red blood cell (RBC) by the Plasmodium parasite defines the start of malaria disease pathogenesis. To date, experimental investigations into invasion have focused predominantly on the role of parasite adhesins or signaling pathways and the identity of binding receptors on the red cell surface. A potential role for signaling pathways within the erythrocyte, which might alter red cell biophysical properties to facilitate invasion, has largely been ignored. The parasite erythrocyte-binding antigen 175 (EBA175), a protein required for entry in most parasite strains, plays a key role by binding to glycophorin A (GPA) on the red cell surface, although the function of this binding interaction is unknown. Here, using real-time deformability cytometry and flicker spectroscopy to define biophysical properties of the erythrocyte, we show that EBA175 binding to GPA leads to an increase in the cytoskeletal tension of the red cell and a reduction in the bending modulus of the cell's membrane. We isolate the changes in the cytoskeleton and membrane and show that reduction in the bending modulus is directly correlated with parasite invasion efficiency. These data strongly imply that the malaria parasite primes the erythrocyte surface through its binding antigens, altering the biophysical nature of the target cell and thus reducing a critical energy barrier to invasion. This finding would constitute a major change in our concept of malaria parasite invasion, suggesting it is, in fact, a balance between parasite and host cell physical forces working together to facilitate entry.erythrocyte | malaria | real-time deformability cytometry | flicker spectroscopy | merozoite M alaria infections cause ∼438,000 deaths per year, most of which are due to the protozoan parasite Plasmodium falciparum (1). Although extensive eradication efforts have helped to reduce the incidence of malaria, the spread of drug resistance is a growing concern and novel treatments are urgently needed (2). Throughout the Plasmodium life cycle, parasites shuttle between replicative and motile life-cycle stages, with the motile forms or "zoites" highly adapted to the invasion of host cells. During the blood stages of infection, the merozoite targets and invades the red blood cell (RBC) rapidly (< 30 s) in a process that involves numerous parasite ligands and host cell receptors (3). Merozoite entry is a multistep process commencing with initial attachment and ending with parasite actomyosin-driven invasion (4). Although extensive cellular and molecular details of each step have been elucidated (5, 6), there is still little mechanistic understanding of the role of each protein involved or the signaling events within the erythrocyte that accompany entry (7).Initial attachment to the RBC surface is likely mediated by merozoite surface proteins. Subsequently, the key signaling and strong attachment interactions between host and parasite membranes are thought to be mediated by two major classes of adhesins released either before or concomitant with inva...

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Sub-resolution lipid domains exist in the plasma membrane and regulate protein diffusion and distribution

Cited by 240 publications

References 48 publications

Prolonged Intake of Dietary Lipids Alters Membrane Structure and T Cell Responses in LDLr−/− Mice

Prolonged Intake of Dietary Lipids Alters Membrane Structure and T Cell Responses in LDLr−/− Mice

The Mechanism of Membrane Disruption by Cytotoxic Amyloid Oligomers Formed by Prion Protein(106–126) Is Dependent on Bilayer Composition

Plasmodium falciparum erythrocyte-binding antigen 175 triggers a biophysical change in the red blood cell that facilitates invasion

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