Unbiased Quantitative Proteomics of Lipid Rafts Reveals High Specificity for Signaling Factors

Membrane lipids were once thought to be homogenously distributed in the 2D surface of a membrane, but the lipid raft theory suggests that cholesterol and sphingolipids partition away from other membrane lipids. Lipid raft theory further implicates these cholesterol-rich domains in many processes suc...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2003-05, Vol.100 (10), p.5813-5818
Main Authors: Foster, Leonard J., de Hoog, Carmen L., Mann, Matthias
Format: Article
Language:English
Subjects:
Biochemistry
Biological Sciences
Cell division
Cell Fractionation
Cell membranes
Centrifugation
Centrifugation, Density Gradient
Cholesterols
Culture Media
Detergents - pharmacology
Filipin - pharmacology
HeLa Cells
Humans
Hydrogen-Ion Concentration
Leucine - metabolism
Lipids
Membrane Microdomains - drug effects
Membrane Microdomains - physiology
Membrane Microdomains - ultrastructure
Membrane Proteins - analysis
Membrane Proteins - genetics
Membranes
Mitochondria
Nystatin - pharmacology
P branes
Proteome
Proteomics
Rafts
Signal Transduction - drug effects
Signal Transduction - physiology
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Summary:Membrane lipids were once thought to be homogenously distributed in the 2D surface of a membrane, but the lipid raft theory suggests that cholesterol and sphingolipids partition away from other membrane lipids. Lipid raft theory further implicates these cholesterol-rich domains in many processes such as signaling and vesicle traffic. However, direct characterization of rafts has been difficult, because they cannot be isolated in pure form. In the first functional proteomic analysis of rafts, we use quantitative high-resolution MS to specifically detect proteins depleted from rafts by cholesterol-disrupting drugs, resulting in a set of 241 authentic lipid raft components. We detect a large proportion of signaling molecules, highly enriched versus total membranes and detergent-resistant fractions, which thus far biochemically defined rafts. Our results provide the first large-scale and unbiased evidence, to our knowledge, for the connection of rafts with signaling and place limits on the fraction of plasma membrane composed by rafts.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0631608100