Protein Association with Membrane Rafts


Membrane rafts are very small and highly dynamic assemblies in cellular membranes enriched in cholesterol and sphingolipids. Some proteins can functionally associate with rafts: peripheral membrane proteins are incorporated into rafts depending on cues such as the presence of a glycosyl‐phosphatidylinositol (GPI) anchor or S‐acylation (palmitoylation); transmembrane proteins can partition into raft domains depending on specific features within their transmembrane domain. Raft association of membrane proteins was originally defined by their resistance to cold Triton X‐100 extraction, which is however insufficient as the sole criterion – more sophisticated methodology such as fluorescence resonance energy transfer (FRET) has to be employed to determine whether and how a given protein interacts with raft structures.

Key Concepts:

  • Membrane rafts are small, dynamic clusters within biological membranes enriched in cholesterol and sphingolipids.

  • Rafts can be coalesced and stabilised to fulfil a biological function, for example, signal transduction or virus budding.

  • Some proteins are capable of partitioning into raft domains.

  • Raft‐targeting features in proteins are glycosyl‐phosphatidylinositol (GPI) anchors, S‐acylation (palmitoylation) and structural motifs in the transmembrane domain.

  • Assessment of detergent‐resistant membranes (DRM), the original biochemical method to analyse raft association of a protein, is artefact‐prone and therefore not suitable to prove raft involvement in a biological process.

  • More sophisticated methodology such as fluorescence resonance energy transfer (FRET) is needed to decipher raft association of a protein.

Keywords: membrane raft; cholesterol; sphingolipid; glycosyl‐phosphatidylinositol (GPI) anchor; S‐acylation/palmitoylation; detergent‐resistant membranes (DRM); fluorescence microscopy; fluorescence resonance energy transfer (FRET); nanoscopy; model membranes

Figure 1.

Lipids and membrane rafts. (a) The major membrane lipids glycerophospholipids (palmitoyl‐oleoyl‐phosphatidylcholine is shown), sphingolipids and cholesterol with their hydrophilic headgroups indicated by a circle. (b) Sphingolipids and cholesterol have the propensity to form a liquid‐ordered membrane phase.

Figure 2.

Cellular membrane rafts. (a) Rafts in resting cells are very small and dynamic. Some proteins can dynamically partition into these rafts (1, GPI‐anchored protein; 2, double acylated protein; 3, transmembrane protein with a hypothetical lipid binding pocket [blue] and/or palmitoylation), others (4, 5) cannot. (b) Rafts can be coalesced to larger, stabilised platforms to fulfil a biological function. Raft proteins (1, 2, 3) are concentrated in rafts by, for example, ligand binding, effectors (yellow) can bind to these platforms. For some prominent examples for raft proteins (1, 2, 3), see Table .

Figure 3.

Covalent lipid modifications of proteins: myristoylation, S‐acylation and isoprenylation. See Table for details.



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Further Reading

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How to Cite close
Veit, Michael, and Thaa, Bastian(Jun 2011) Protein Association with Membrane Rafts. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0023404]