Lipid rafts serve as signaling platforms for mGlu1 receptor-mediated calcium signaling in association with caveolin

Background: Group I metabotropic glutamate receptors (mGlu1/5 receptors) have important roles in synaptic activity in the central nervous system. They modulate neuronal excitability by mobilizing intracellular Ca2+ following receptor activation. Also, accumulating evidence has indicated the association of Ca2+ signaling with lipid rafts. Caveolin, an adaptor protein found in a specialized subset of lipid rafts, has been reported to promote the localization of membrane proteins to lipid rafts. Results: In the present study, we investigated the role of lipid rafts on the mGlu1 alpha receptor-mediated Ca2+ signaling in association with caveolin in hippocampal primary neurons and HEK293 cells. We show that the disruption of lipid rafts using methyl-beta-cyclodextrin markedly decreased mGlu1 alpha receptor-mediated Ca2+ transients and lipid rafts localization of the receptor. Furthermore, transfection of mGlu1 alpha receptor with mutated caveolin-binding domain reduced localization of the receptor to lipid rafts. Also, application of a peptide blocker of mGlu1 alpha receptor and caveolin binding reduced the Ca2+ signaling and the lipid rafts localization. Conclusions: Taken together, these results suggest that the binding of mGlu1 alpha receptor to caveolin is crucial for its lipid rafts localization and mGlu1 alpha receptor-mediated Ca2+ transients.