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

Rémi Lasserre; Xiao-Jun Guo; Fabien Conchonaud; Yannick Hamon; Omar Hawchar; Anne-Marie Bernard; Saïdi M'Homa Soudja; Pierre-François Lenne; Hervé Rigneault; Daniel Olive; Georges Bismuth; Jacques A Nunès; Bernard Payrastre; Didier Marguet; Hai-Tao He

doi:10.1038/nchembio.103

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

Nat Chem Biol. 2008 Sep;4(9):538-47. doi: 10.1038/nchembio.103. Epub 2008 Jul 20.

Authors

Rémi Lasserre¹, Xiao-Jun Guo, Fabien Conchonaud, Yannick Hamon, Omar Hawchar, Anne-Marie Bernard, Saïdi M'Homa Soudja, Pierre-François Lenne, Hervé Rigneault, Daniel Olive, Georges Bismuth, Jacques A Nunès, Bernard Payrastre, Didier Marguet, Hai-Tao He

Affiliation

¹ Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Parc scientifique de Luminy, Case 906, F-13288 Marseille Cedex 09, France.

PMID: 18641634
DOI: 10.1038/nchembio.103

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
COS Cells
Chlorocebus aethiops
Cholesterol / biosynthesis
Green Fluorescent Proteins / metabolism
Humans
Jurkat Cells
Membrane Microdomains* / enzymology
Membrane Microdomains* / metabolism
Membrane Microdomains* / physiology
Mice
Phosphatidylinositol 3-Kinases / metabolism*
Proto-Oncogene Proteins c-akt / metabolism*
Signal Transduction* / physiology
Spectrometry, Fluorescence
Sphingolipids / antagonists & inhibitors
Sphingolipids / biosynthesis
T-Lymphocytes / metabolism

Substances

Sphingolipids
Green Fluorescent Proteins
Cholesterol
Proto-Oncogene Proteins c-akt

Associated data

PubChem-Substance/49854209
PubChem-Substance/49854210
PubChem-Substance/49854211
PubChem-Substance/49854212
PubChem-Substance/49854213
PubChem-Substance/49854214
PubChem-Substance/49854215
PubChem-Substance/49854216
PubChem-Substance/49854217
PubChem-Substance/49854218
PubChem-Substance/49854219
PubChem-Substance/49854220
PubChem-Substance/49854221
PubChem-Substance/49854222
PubChem-Substance/49854223
PubChem-Substance/49854224
PubChem-Substance/49854225
PubChem-Substance/49854226
PubChem-Substance/49854227
PubChem-Substance/49854228
PubChem-Substance/49854229
PubChem-Substance/49854230