Polysialic acid chains are a post-translational modification found mainly on NCAM. These highly charged polymers decrease cell adhesion and promote migration, and have been suggested to contribute to both neuronal plasticity and cancer metastasis. The NCAM transmembrane adhesion molecule is found clustered in lipid rafts, highly ordered regions of the plasma membrane important for NCAM signaling. Because polysialylated NCAM is enriched in lipid rafts compared to unmodified NCAM, Sapoń and colleagues investigated whether polysialic acid modification may play a role in recruiting NCAM to lipid rafts in a recent report in BBA – Biomembranes.
Using Dilinoleyl DiI (also called FAST DiI™) fluorogenic membrane dye to label liquid-fluid membrane regions and fluorescent cholera toxin to label lipid rafts, the authors used FRET spectroscopy to analyze the localization of antibody-labeled polysialic acid chains in model membranes and plasma membranes. They showed that polysialic acid chains have a higher affinity for lipid-ordered raft regions compared to lipid-disordered membrane regions, suggesting that polysialic acid modification may help recruit NCAM to lipid rafts.