Molecular characterization of the detergent-insoluble cholesterol-rich membrane microdomain (raft) of the central nervous system

Many fundamental neurological issues such as neuronal polarity, the formation and remodeling of synapses, synaptic transmission, and the pathogenesis of the neuronal cell death are closely related to the membrane dynamics. The elucidation of functional roles of a detergent-insoluble cholesterol-rich domain (raft) could therefore provide good clues to the molecular understanding of these important phenomena, for the participation of the raft in the fundamental cell functions, such as signal transduction and selective transport of lipids and proteins, has been elucidated in nonneural cells. Interestingly, the brain is rich in raft and the brain-derived raft differs in its lipid and protein components from other tissue-derived rafts. Since many excellent reviews are written on the membrane lipid dynamics of this microdomain, signal transduction, and neuronal glycolipids, we review on the characterization of the raft proteins recovered in the detergent-insoluble low-density fraction from rat brain. Special focus is addressed on the biochemical characterization of a neuronal enriched protein, NAP-22, for the lipid organizing activity of this protein has become increasingly clear.