Important role of raft aggregation in the signaling events of cold-induced platelet activation

Karine Gousset, Nelly M. Tsvetkova, John H. Crowe, Fern Tablin

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

When human platelets are chilled below 20°C, they undergo cold-induced activation. We have previously shown that cold activation correlates with the main phospholipid phase transition (10-20°C) and induces the formation of large raft aggregates. In addition, we found that the glycoprotein CD36 is selectively enriched within detergent-resistant membranes (DRMs) of cold-activated platelets and is extremely sensitive to treatment with methyl-β-cyclodextrin (MβCD). Here, we further studied the partitioning of downstream signaling molecules within the DRMs. We found that the phospholipase Cγ2 (PLCγ2) and the protein tyrosine kinase Syk do not partition exclusively within the DRMs, but their distribution is perturbed by cholesterol extraction. In addition, PLCγ2 activity increases in cold-activated cells compared to resting platelets and is entirely inhibited after treatment with MβCD. The Src-family protein tyrosine kinases Src and Lyn preferentially partition within the DRMs and are profoundly affected by removal of cholesterol. These kinases are non-redundant in cold-activation. CD36, active Lyn, along with inactive Src and PLCγ2 co-localize in small raft complexes in resting platelets. Cold-activation induces raft aggregation, resulting in changes in the activity of these proteins. These data suggest a crucial role of raft aggregation in the early events of cold-induced platelet activation.

Original languageEnglish (US)
Pages (from-to)7-15
Number of pages9
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1660
Issue number1
DOIs
StatePublished - Jan 28 2004

Keywords

  • Cyclodextrin
  • Microdomain
  • Platelet
  • Protein tyrosine kinase
  • Raft
  • Signaling

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Biophysics

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