Revaluation of the role of cholesterol in stabilizing rafts implicated in T cell receptor signaling

T lymphocytes contain two kinetic pools of cholesterol extractable with methyl-β-cyclodextrin (m-β-CD): a fast pool (31.5%, t 1 / 2 = 17 s) and a slow pool (68.5%, t 1 / 2 = 15 min). Purification of detergent-resistant membranes (DRMs) shows that the fast pool corresponds to buoyant cholesterol. Cho...

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Bibliographic Details
Published in:Cellular signalling 2006, Vol.18 (1), p.105-122
Main Authors: Rouquette-Jazdanian, Alexandre K., Pelassy, Claudette, Breittmayer, Jean-Philippe, Aussel, Claude
Format: Article
Language:English
Subjects:
Adult
beta-Cyclodextrins - pharmacology
CD3 Complex - metabolism
CD4-Positive T-Lymphocytes - drug effects
CD4-Positive T-Lymphocytes - physiology
Cell Membrane - drug effects
Cell Membrane - metabolism
Cholesterol
Cholesterol - metabolism
Cholesterol - physiology
Cholesterol oxidase
Detergent-resistant membranes (DRMs)
Dose-Response Relationship, Drug
Humans
Jurkat Cells
Membrane Microdomains - drug effects
Membrane Microdomains - physiology
Methyl-β-cyclodextrin
Oxidation-Reduction
Phospholipase C gamma - metabolism
Phosphorylation
Rafts
Receptors, Antigen, T-Cell - drug effects
Receptors, Antigen, T-Cell - physiology
Reference Values
Signal Transduction - drug effects
Signal Transduction - physiology
T lymphocyte activation
Time Factors
Tyrosine - metabolism
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Summary:T lymphocytes contain two kinetic pools of cholesterol extractable with methyl-β-cyclodextrin (m-β-CD): a fast pool (31.5%, t 1 / 2 = 17 s) and a slow pool (68.5%, t 1 / 2 = 15 min). Purification of detergent-resistant membranes (DRMs) shows that the fast pool corresponds to buoyant cholesterol. Cholesterol extraction of the fast pool (i.e. cholesterol from rafts) still allows the buoyancy of signaling proteins and their phosphorylation under CD3 stimulation. Cholesterol depletion of the slow pool (i.e. cholesterol from membranes other than rafts) is accompanied by the extraction of the whole raft followed by the inhibition of CD3-induced tyrosine-phosphorylations. Cholesterol oxidase (COase) allows a specific oxidation of raft cholesterol into cholestenone. Cholestenone leaves the DRMs and accumulates as Triton X-100-soluble material. Specific cholesterol-rich raft disruption by COase does not inhibit the activation of either Jurkat cells or T CD4 + lymphocytes. Our study challenges the real role of cholesterol-rich rafts in CD3/TCR signaling and suggests that a cholesterol-poor subtype of rafts is involved in signal transmission via the TCR.
ISSN:0898-6568
1873-3913
DOI:10.1016/j.cellsig.2005.03.024