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Limited cholesterol depletion causes aggregation of plasma membrane lipid raftsinducing T cell activation
Stockholms universitet, Wenner-Grens institut.
Stockholms universitet, Wenner-Grens institut.
Stockholms universitet, Wenner-Grens institut.
Stockholms universitet, Wenner-Grens institut.
2010 (Engelska)Ingår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, ISSN 1388-1981, E-ISSN 1879-2618, Vol. 1801, nr 6, s. 625-634Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Acute cholesterol depletion is generally associated with decreased or abolished T cell signalling but it can also cause T cell activation. This anomaly has been addressed in Jurkat T cells using progressive cholesterol depletion with methyl-beta-cyclodextrin (MBCD). At depletion levels higher than 50% there is substantial cell death, which explains reports of signalling inhibition. At 10–20% depletion levels, tyrosine phosphorylation is increased, ERK is activated and there is a small increase in cytoplasmic Ca2+. Peripheral actin polymerisation is also triggered by limited cholesterol depletion. Strikingly, the lipid raft marker GM1 aggregates upon cholesterol depletion and these aggregated domains concentrate the signalling proteins Lck and LAT, whereas the opposite is true for the non lipid raft marker the transferrin receptor. Using PP2, an inhibitor of Src family kinase activation, it is demonstrated that the lipid raft aggregation occurs independently of and thus upstream of the signalling response. Upon cholesterol depletion there is an increase in overall plasma membrane order, indicative of more ordered domains forming at the expense of disordered domains. That cholesterol depletion and not unspecific effects of MBCD was behind the reported results was confirmed by performing all experiments with MBCD–cholesterol, when no net cholesterol extraction took place. We conclude that non-lethal cholesterol depletion causes the aggregation of lipid rafts which then induces T cell signalling.

Ort, förlag, år, upplaga, sidor
2010. Vol. 1801, nr 6, s. 625-634
Nyckelord [en]
Actin, Cholesterol, Colocalization, Lipid raft, Membrane order, Methyl-beta-cyclodextrin, T cell signalling
Nationell ämneskategori
Cellbiologi
Forskningsämne
cellbiologi
Identifikatorer
URN: urn:nbn:se:uu:diva-188322DOI: 10.1016/j.bbalip.2010.02.003ISI: 000277912600003OAI: oai:DiVA.org:uu-188322DiVA, id: diva2:577258
Tillgänglig från: 2010-04-09 Skapad: 2012-12-14 Senast uppdaterad: 2017-12-06Bibliografiskt granskad

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