Key Points
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Ten years ago, the lipid raft field was suffering from ambiguous methodology and imprecise nomenclature.
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New high-resolution imaging methods are now giving insights into raft dynamics. Together with other studies, this has led to changes in our concept of rafts.
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Rafts in plasma membranes can be characterized by three different states: dynamic nanoscale assemblies, raft platforms stabilized by oligomerization and micrometre-scale phase separation.
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Lipidomics is beginning to give comprehensive views of the lipid composition of raft domains.
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Three examples of roles that rafts have in cellular function are: T cell signalling, HIV assembly and membrane trafficking.
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A key open issue for the field is how lipids interact with integral raft proteins.
Abstract
Ten years ago, we wrote a Review on lipid rafts and signalling in the launch issue of Nature Reviews Molecular Cell Biology. At the time, this field was suffering from ambiguous methodology and imprecise nomenclature. Now, new techniques are deepening our insight into the dynamics of membrane organization. Here, we discuss how the field has matured and present an evolving model in which membranes are occupied by fluctuating nanoscale assemblies of sphingolipids, cholesterol and proteins that can be stabilized into platforms that are important in signalling, viral infection and membrane trafficking.
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Acknowledgements
We thank H. He for critically reading the manuscript and the members of the K.S. laboratory for input, especially D. Lingwood and I. Levental. Work in the K.S. laboratory was supported by the EUFP6 PRISM grant LSHB-CT2007–037,740, DFG Schwerpunktprogramm1175, the BMBF BioChance Plus grant 0313,827 and the BMBF ForMaT grant 03FO1212.
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Kai Simons is a co-founder of the biotechnology company JADO Technologies, which specializes in membrane invention technologies, including lipid raft modulation.
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Glossary
- Caveola
-
A 50–80-nm, flask-shaped pit that forms in the plasma membrane and is enriched in caveolins, cavins, sphingolipids and cholesterol.
- Förster resonance energy transfer
-
A fluorescence-based method for detecting interactions between fluorophores that are <10 nm apart. It is dependent on the spectral overlap between donor and acceptor chromophores and uses non-radiative energy transfer from an excited donor molecule to excite an acceptor molecule.
- Fluorescence polarization anisotropy
-
A technique to measure rotational diffusion using changes in fluorescence polarization that are due to fluorophore rotation.
- GPI-anchored protein
-
(Glycosyl phosphatidylinositol-anchored protein). One of a class of proteins that become post-translationally linked to GPI in the lumen of the ER.
- Total internal reflection fluorescence (TIRF) microscopy
-
An optical technique based on evanescent wave illumination (∼150 nm into the sample) that is created by a totally internally reflected beam at the glass–water interface.
- Quantum dot
-
A nanoscale semiconductor crystal used as a label in fluorescence microscopy owing to its high emission and photostability.
- Fluorescence correlation spectroscopy
-
A technique that measures diffusion by correlating the fluorescence signal of a diffusing fluorophore with time.
- Stimulated emission depletion
-
A nanoscopic technique that uses a red-shifted beam to deplete the emission of the periphery of the excitation spot and create a smaller excitation region, thus overcoming the diffraction limit.
- PALM and STORM
-
(Photoactivated localization microscopy and stochastic optical reconstruction microscopy). Super-resolution microscopy techniques that use stochastically photoactivated fluorescent probes to reconstitute the full image from individual point spread functions.
- Near-field scanning optical microscopy
-
A super-resolution technique that exploits the evanescent wave near the surface of the sample by placing the detector close to the sample.
- Glycosphingolipid
-
A lipid that contains at least one sugar residue and a ceramide (N-acylated sphingoid).
- Palmitoylation
-
The reversible covalent attachment of fatty acids to Cys residues of membrane proteins, which promotes their membrane association.
- Major histocompatibility complex
-
A complex of genetic loci in higher vertebrates that encodes a family of cellular antigens that allow the immune system to recognize self from non-self.
- Lipid shell
-
A model proposing that specific membrane proteins bind to complexes of cholesterol and sphingolipids or laterally organize specific contacting lipids.
- STALL
-
(Stimulation-induced temporary arrest of lateral diffusion). The cholesterol-assisted, sub-second trapping of GPI-anchored signalling proteins with downstream signalling proteins.
- Myristate
-
A group that is attached to a protein through an amide bond by the irreversible, co-translational process of myristoylation. This is an important modification for membrane targeting.
- Shiga toxin
-
One of a family of protein toxins produced by bacteria that can cause dysentery.
- Line energy
-
The energy arising from the unfavourable interaction or 'tension' of two phase- segregating membrane domains. It is the product of line tension and interaction length.
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Simons, K., Gerl, M. Revitalizing membrane rafts: new tools and insights. Nat Rev Mol Cell Biol 11, 688–699 (2010). https://doi.org/10.1038/nrm2977
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DOI: https://doi.org/10.1038/nrm2977
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