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Pré-Publication, Document De Travail Année : 2006

A physical and functional link between cholesterol and tetraspanins.

Résumé

By interacting with each others, the tetraspanins are thought to assemble a network of molecular interactions, the tetraspanin web. These tetraspanin/tetraspanin interactions involve in part the palmitoylation of the proteins. We show that tetraspanins interact with cholesterol as indicated by the precipitation of tetraspanin/tetraspanin complexes by digitonin, a cholesterol-precipitating reagent, and the labeling of the tetraspanins CD9, CD81 and CD82 with a photoactivatable cholesterol in vivo. Cholesterol may participate to the interaction of tetraspanins with each other since digitonin-precipitation of tetraspanins was correlated with their mutual interaction, and because these interactions were disrupted following cholesterol depletion by methyl-beta-cyclodextrin (MbetaCD) treatment, or cholesterol sequestration by saponin. A mutant CD9 molecule lacking all palmitoylation sites was not precipitated by digitonin under conditions in which wild-type CD9 was precipitated, indicating a role of palmitoylation for the interaction with cholesterol. Finally, upon ligation of tetraspanins on the surface of a lymphoid B cell line, the tyrosine phosphorylation of several proteins, including the vav nucleotide exchange factor, was inhibited when cells were pretreated with MbetaCD, and increased when they were treated with MbetaCD/cholesterol complexes. Thus, there is a physical and functional link between tetraspanins and cholesterol.
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Dates et versions

hal-00112786 , version 1 (09-11-2006)

Identifiants

  • HAL Id : hal-00112786 , version 1
  • PUBMED : 12938224

Citer

S. Charrin, S. Manie, C. Thiele, M. Billard, D. Gerlier, et al.. A physical and functional link between cholesterol and tetraspanins.. 2006. ⟨hal-00112786⟩
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