title: Raft nanodomains contribute to Akt/PKB plasma membrane recruitment and activation.
abstract: 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.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Parc scientifique de Luminy, Case 906, F-13288 Marseille Cedex 09, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Lasserre
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Guo
authors.forename: Fabien
authors.initials: F
authors.lastname: Conchonaud
authors.forename: Yannick
authors.initials: Y
authors.lastname: Hamon
authors.forename: Omar
authors.initials: O
authors.lastname: Hawchar
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Bernard
authors.forename: Saïdi M'Homa
authors.initials: SM
authors.lastname: Soudja
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Lenne
authors.forename: Hervé
authors.initials: H
authors.lastname: Rigneault
authors.forename: Daniel
authors.initials: D
authors.lastname: Olive
authors.forename: Georges
authors.initials: G
authors.lastname: Bismuth
authors.forename: Jacques A
authors.initials: JA
authors.lastname: Nunès
authors.forename: Bernard
authors.initials: B
authors.lastname: Payrastre
authors.forename: Didier
authors.initials: D
authors.lastname: Marguet
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: He
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000096:biosynthesis; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D021962:Membrane Microdomains / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013050:Spectrometry, Fluorescence; D013107:Sphingolipids / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D002784:Cholesterol; D049452:Green Fluorescent Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D013107:Sphingolipids