scholarly journals Role of the membrane cholesterol-glycosphingolipid complex as a ‘transistor’ to regulate GSL receptor function and signaling of both lipids

2017 ◽  
Author(s):  
Anton Novak ◽  
Clifford Lingwood
Keyword(s):  
Ligand Binding ◽  
Lipid Rafts ◽  
Clinical Importance ◽  
Membrane Lipid ◽  
Signal Pathways ◽  
Membrane Cholesterol ◽  
Plasma Membrane Lipid ◽  
Dependent Signal ◽  
Partial Dissociation ◽  
Exogenous Ligand

AbstractCholesterol and glycosphingolipids (GSL) are the major species that accumulate in plasma membrane lipid rafts. These complexes imbue the membrane with increased order, which in turn, plays a central role in the transmembrane signaling foci lipid rafts provide. In addition, both GSL and cholesterol binding can mediate (separate) signal pathways. We have shown that cholesterol and GSLs however, form a complex in which the GSL sugar is reoriented from a membrane perpendicular to parallel format, becoming largely unavailable for exogenous ligand binding. Similarly, the steroid hydroxyl is masked, restricting access of cholesterol ligands. This was observed in model and cell membranes and in human tumour frozen tissue sections. We now show the order of exogenous ligand binding plays a significant role to determine the extent of GSL or cholesterol receptor activity. Ligand binding to cholesterol enhances subsequent GSL recognition and vice versa, suggesting that ligand binding to “free” receptor (membrane perpendicular GSL carbohydrate, nonmasked cholesterol) can result in partial dissociation of the GSL/cholesterol complex to allow additional GSL ligand and cholesterol ligand binding. Since many GSLs can complex with membrane cholesterol, the binding of a single cholesterol ligand may unmask cholesterol-complexed GSL for increased binding of both a single or multiple GSL-specific ligands. We show that multiple cholesterol-masked GSLs can be coincident in tissues. This provides a mechanism for GSL-dependent signal amplification and diversification, representing a biological ‘transistor’, regulating amplitude and potentially, diversity of GSL signaling. The process represents a new mechanism of ‘cross-talk’ between GSL and cholesterol signaling. This is of clinical importance since we have found cholesterol/GSL masking applies to monoclonal anti GSL antibodies in development and in current use as antineoplastic therapeutics.

1P-0227 Apolipoprotein A-1 interaction with plasma membrane lipid rafts controls cholesterol export from macrophages

2003 ◽  
Vol 4 (2) ◽  
pp. 69 ◽  
Author(s):  
W. Jessup ◽  
K. Gaus ◽  
L. Kritharides ◽  
A. Boettcher ◽  
W. Drobnik ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Lipid Rafts ◽  
Membrane Lipid ◽  
Apolipoprotein A ◽  
Plasma Membrane Lipid

scholarly journals Moderate Static Magnetic Field (6 mT)-Induced Lipid Rafts Rearrangement Increases Silver NPs Uptake in Human Lymphocytes

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1398
Author(s):  
Cristian Vergallo ◽  
Elisa Panzarini ◽  
Bernardetta Anna Tenuzzo ◽  
Stefania Mariano ◽  
Ada Maria Tata ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Human Lymphocytes ◽  
Peripheral Blood Lymphocytes ◽  
Membrane Lipid ◽  
Membrane Perturbation ◽  
Plasma Membrane Lipid ◽  
Silver Nps ◽  
Surface Ligand

One of the most relevant drawbacks in medicine is the ability of drugs and/or imaging agents to reach cells. Nanotechnology opened new horizons in drug delivery, and silver nanoparticles (AgNPs) represent a promising delivery vehicle for their adjustable size and shape, high-density surface ligand attachment, etc. AgNPs cellular uptake involves different endocytosis mechanisms, including lipid raft-mediated endocytosis. Since static magnetic fields (SMFs) exposure induces plasma membrane perturbation, including the rearrangement of lipid rafts, we investigated whether SMF could increase the amount of AgNPs able to pass the peripheral blood lymphocytes (PBLs) plasma membrane. To this purpose, the effect of 6-mT SMF exposure on the redistribution of two main lipid raft components (i.e., disialoganglioside GD3, cholesterol) and on AgNPs uptake efficiency was investigated. Results showed that 6 mT SMF: (i) induces a time-dependent GD3 and cholesterol redistribution in plasma membrane lipid rafts and modulates gene expression of ATP-binding cassette transporter A1 (ABCA1), (ii) increases reactive oxygen species (ROS) production and lipid peroxidation, (iii) does not induce cell death and (iv) induces lipid rafts rearrangement, that, in turn, favors the uptake of AgNPs. Thus, it derives that SMF exposure could be exploited to enhance the internalization of NPs-loaded therapeutic or diagnostic molecules.

scholarly journals Membrane lipid rafts are disturbed in the response of rat skeletal muscle to short-term disuse

2017 ◽  
Vol 312 (5) ◽  
pp. C627-C637 ◽  
Author(s):  
Alexey M. Petrov ◽  
Violetta V. Kravtsova ◽  
Vladimir V. Matchkov ◽  
Alexander N. Vasiliev ◽  
Andrey L. Zefirov ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Motor Nerve ◽  
Membrane Lipid ◽  
Hindlimb Suspension ◽  
Cholera Toxin B Subunit ◽  
Plasma Membrane Lipid ◽  
Intracellular Ca

Marked loss of skeletal muscle mass occurs under various conditions of disuse, but the molecular and cellular mechanisms leading to atrophy are not completely understood. We investigate early molecular events that might play a role in skeletal muscle remodeling during mechanical unloading (disuse). The effects of acute (6–12 h) hindlimb suspension on the soleus muscles from adult rats were examined. The integrity of plasma membrane lipid rafts was tested utilizing cholera toxin B subunit or fluorescent sterols. In addition, resting intracellular Ca2+ level was analyzed. Acute disuse disturbed the plasma membrane lipid-ordered phase throughout the sarcolemma and was more pronounced in junctional membrane regions. Ouabain (1 µM), which specifically inhibits the Na-K-ATPase α2 isozyme in rodent skeletal muscles, produced similar lipid raft changes in control muscles but was ineffective in suspended muscles, which showed an initial loss of α2 Na-K-ATPase activity. Lipid rafts were able to recover with cholesterol supplementation, suggesting that disturbance results from cholesterol loss. Repetitive nerve stimulation also restores lipid rafts, specifically in the junctional sarcolemma region. Disuse locally lowered the resting intracellular Ca2+ concentration only near the neuromuscular junction of muscle fibers. Our results provide evidence to suggest that the ordering of lipid rafts strongly depends on motor nerve input and may involve interactions with the α2 Na-K-ATPase. Lipid raft disturbance, accompanied by intracellular Ca2+ dysregulation, is among the earliest remodeling events induced by skeletal muscle disuse.

Manipulating membrane lipid profiles to restore T-cell function in autoimmunity

2015 ◽  
Vol 43 (4) ◽  
pp. 745-751 ◽  
Author(s):  
Kirsty E. Waddington ◽  
Elizabeth C. Jury
Keyword(s):  
T Cell ◽  
Lipid Rafts ◽  
Lupus Erythematosus ◽  
Cell Function ◽  
Immune Cell ◽  
Membrane Lipids ◽  
Membrane Lipid ◽  
Plasma Membrane Lipid ◽  
Disease Systemic Lupus Erythematosus ◽  
Acyl Chains

Plasma membrane lipid rafts are heterogeneous cholesterol and glycosphingolipid (GSL)-enriched microdomains, within which the tight packing of cholesterol with the saturated-acyl chains of GSLs creates a region of liquid-order relative to the surrounding disordered membrane. Thus lipid rafts govern the lateral mobility and interaction of membrane proteins and regulate a plethora of signal transduction events, including T-cell antigen receptor (TCR) signalling. The pathways regulating homoeostasis of membrane cholesterol and GSLs are tightly controlled and alteration of these metabolic processes coincides with immune cell dysfunction as is evident in atherosclerosis, cancer and autoimmunity. Indeed, membrane lipid composition is emerging as an important factor influencing the ability of cells to respond appropriately to microenvironmental stimuli. Consequently, there is increasing interest in targeting membrane lipids or their metabolic control as a novel therapeutic approach to modulate immune cell behaviour and our recent work demonstrates that this is a promising strategy in T-cells from patients with the autoimmune disease systemic lupus erythematosus (SLE).

scholarly journals Analysis of Detergent-Resistant Membranes in Arabidopsis. Evidence for Plasma Membrane Lipid Rafts

2004 ◽  
Vol 137 (1) ◽  
pp. 104-116 ◽  
Author(s):  
Georg H.H. Borner ◽  
D. Janine Sherrier ◽  
Thilo Weimar ◽  
Louise V. Michaelson ◽  
Nathan D. Hawkins ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Lipid Rafts ◽  
Membrane Lipid ◽  
Plasma Membrane Lipid ◽  
Detergent Resistant Membranes

scholarly journals Cell-To-Cell Variability in Plasma Membrane Lipid Rafts

2013 ◽  
Vol 104 (2) ◽  
pp. 191a-192a
Author(s):  
Roland Schwarzer ◽  
Silvia Scolari ◽  
Reismann David ◽  
Rolf Schwarzer ◽  
Andreas Herrmann
Keyword(s):  
Plasma Membrane ◽  
Lipid Rafts ◽  
Membrane Lipid ◽  
Plasma Membrane Lipid ◽  
Cell To Cell Variability

Interaction of phosphatidylinositolglycan(-peptides) with plasma membrane lipid rafts triggers insulin-mimetic signaling in rat adipocytes

2002 ◽  
Vol 408 (1) ◽  
pp. 7-16 ◽  
Author(s):  
Günter Müller ◽  
Christian Jung ◽  
Wendelin Frick ◽  
Wolfhard Bandlow ◽  
Werner Kramer
Keyword(s):  
Plasma Membrane ◽  
Lipid Rafts ◽  
Membrane Lipid ◽  
Rat Adipocytes ◽  
Insulin Mimetic ◽  
Plasma Membrane Lipid

Interaction of phosphoinositolglycan(-peptides) with plasma membrane lipid rafts of rat adipocytes

2002 ◽  
Vol 408 (1) ◽  
pp. 17-32 ◽  
Author(s):  
Günter Müller ◽  
Nils Hanekop ◽  
Werner Kramer ◽  
Wolfhard Bandlow ◽  
Wendelin Frick
Keyword(s):  
Plasma Membrane ◽  
Lipid Rafts ◽  
Membrane Lipid ◽  
Rat Adipocytes ◽  
Plasma Membrane Lipid

Membrane lipid rafts are required for D2 dopamine receptor signaling

2011 ◽  
Vol 26 (S2) ◽  
pp. 910-910 ◽  
Author(s):  
D. Sibley ◽  
L. Hazelwood ◽  
R. Roof ◽  
R.B. Free ◽  
Y. Han ◽  
...  
Keyword(s):  
Dopamine Receptor ◽  
Lipid Rafts ◽  
Lipid Raft ◽  
Gradient Centrifugation ◽  
Membrane Lipid ◽  
Receptor Protein ◽  
Membrane Microdomains ◽  
Membrane Cholesterol ◽  
Camp Accumulation ◽  
D2 Dopamine Receptor

IntroductionLipid rafts are specialized membrane microdomains enriched in cholesterol and sphingolipids and are important in the organization of receptor-protein complexes and the regulation of signaling.Objective/aimsGiven the emerging significance of lipids with respect to receptor structure and activation, we investigated the role of lipid rafts and membrane cholesterol on D2 dopamine receptor (DAR) signaling. As the D2 DAR is the molecular target for all antipsychotic drugs, more information about its signaling may help refine therapeutics for schizophrenia.MethodsD2 DAR constructs were expressed in HEK293T cells. Sucrose density fractionation resolved lipid rafts from other membrane components. Methyl-β-cyclodextrin (MCD) was used to deplete membrane cholesterol and to disrupt lipid rafts.ResultsDetergent solubilization followed by sucrose gradient centrifugation resolved lipid rafts from heavier membrane fractions. The D2 DAR was equally distributed amongst both the lipid raft and heavier membrane fractions. Pretreatment with MCD, however, eliminated both lipid raft markers and the D2 DAR from lipid raft fractions, although the receptor was still found in heavier membrane fractions. We also found that MCD treatment abolished D2 DAR-mediated inhibition of cAMP accumulation. In contrast D1 DAR-stimulated cAMP accumulation was unaffected by MCD treatment.ConclusionsOur current results show that the D2 DAR is distributed in multiple membrane microdomains, including cholesterol-rich lipid rafts. We found that extraction of cholesterol disrupted lipid rafts and also an eliminated D2 DAR-mediated signaling. Thus, we hypothesize that lipid rafts are critical for D2 DAR signaling to occur.

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