Raft nanodomains contribute to Akt/PKB plasma membrane recruitment and activation

• DOI: 10.1038/nchembio.103
• Publication Date: 2008-07-20T17:11:32Z
• Authors: Rémi Lasserre; Xiao-Jun Guo; Fabien Conchonaud; Yannick Hamon; Omar Hawchar; Anne-Marie Bernard; Saïdi M'Homa Soudja; Pierre-François L...; Hervé Rigneault; Daniel Olive; Georges Bismuth; Jacques A Nunès; Bernard Payrastre; Didier Marguet; Hai-Tao He
• Keywords: Lipid raft; Sphingolipid; Raft; Membrane biology; Cell Signaling; Cell membrane

Membrane rafts are thought to be sphingolipid- and cholesterol-dependent lateral assemblies involved in diverse cellular functions. Their biological roles and even their existence, however, remain controversial. Using an original fluorescence correlation spectroscopy strategy that recently enabled us to identify nanoscale membrane organizations in live cells, we report here that highly dynamic nanodomains exist in both the outer and inner leaflets of the plasma membrane. Through specific inhibition of biosynthesis, we show that sphingolipids and cholesterol are essential and act in concert for formation of nanodomains, thus corroborating their raft nature. Moreover, we find that nanodomains play a crucial role in triggering the phosphatidylinositol-3 kinase/Akt signaling pathway, by facilitating Akt recruitment and activation upon phosphatidylinositol-3,4,5-triphosphate accumulation in the plasma membrane. Thus, through direct monitoring and controlled alterations of rafts in living cells, we demonstrate that rafts are critically involved in the activation of a signaling axis that is essential for cell physiology.