The gamma-aminobutyric acid receptor B, but not the metabotropic glutamatereceptor type-1, associates with lipid rafts in the rat cerebellum

Recent evidence suggests that specialized microdomains, called lipid rafts, exist within plasma membranes. These domains are enriched in cholesterol a nd sphingolipids and are resistant to non-ionic detergent-extraction at 4 d egreesC. They contain specific populations of membrane proteins, and can ch ange their size and composition in response to cellular signals, resulting in activation of signalling cascades. Here, we demonstrate that both the me tabotropic gamma -aminobutyric acid receptor B (GABA(B) receptor) and the m etabotropic glutamate receptor-1 from rat cerebellum are insoluble in the n on-ionic detergent Triton X-100. However, only the GABA(B) receptor associa tes with raft fractions isolated from rat brain by sucrose gradient centrif ugation. Moreover, increasing the stringency of isolation by decreasing the protein : detergent ratio caused an enrichment of the GABA(B) receptor in raft fractions. In contrast, depletion of cholesterol from cerebellar membr anes by either saponin or methyl-beta -cyclodextrin treatment, which solubi lize known raft markers, also increased the solubility of the GABA(B) recep tor. These properties are all consistent with an association of the GABA(B) receptor with lipid raft microdomains.