Lipid Raft and Platelet SNARE Machinery

Lipid rafts are defined as insoluble areas in the cell membrane, resistant to non-ionic detergents. These areas, which are also called detergent-resistant membranes (DRMs), and are enriched in glycosphingolipids, saturated phospholipids and cholesterol, have been identified in several cell types including platelets. Initially, they were believed to be responsible for the intercellular transport of glycosyl phosphatidylinositol (GPI)-anchored proteins to the apical surface in polarized cells [1,2]. However, over the decades, rafts have increasingly been recognized as membrane microdomains, and found to play a critical role in the control of several cellular activation processes. Thus, very divergent proteins such as Src family kinases, caveolins, palmitoylated proteins such as G proteins, GPI-anchored proteins such as Thy-1 and alkaline phosphatases, tetraspannin proteolipids and various signaling molecules have all been shown to be associated with lipid rafts. Different types of rafts coexist at the plasma membrane with functionally distinct lipid composition [3]. Furthermore, lipid rafts are not only found at the plasma membrane, but also as part of the internal membrane of granules, Golgi complex and even phagosomes [4,5]. Evidence for a functional role of lipid rafts in platelets is very recent: Gousset et al. [6] have shown that during cold-induced platelet activation, rafts cluster into larger aggregates, a reversible process depending on platelet activation. These authors showed raft aggregation to be dependent on the presence of cholesterol in the membrane, and further identified the presence of CD36 in DRMs. Using fluorescence microscopy of platelets being activated with thrombin and collagen, large fluorescent clusters of lipid rafts were formed, leading these investigators to conclude that raft aggregation is triggered by platelet activation, suggestive of a role for microdomains in platelet signaling [6].