Protein Association with Membrane Rafts

Abstract

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.

Cholesterol modulates the cellular localization of Orai1 channels and its disposition among membrane domains

“…The functions of several SOCE components such as STIM1, Orai1 channels and TRPC1 channels are regulated by its interaction with PM domains enriched in cholesterol (the so-called lipid rafts) [19,29,39–42]. …”