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 Ca(2+) following receptor activation. Also, accumulating evidence has indicated the association of Ca(2+) 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 mGlu1α receptor-mediated Ca(2+) signaling in association with caveolin in hippocampal primary neurons and HEK293 cells. We show that the disruption of lipid rafts using methyl-β-cyclodextrin markedly decreased mGlu1α receptor-mediated Ca(2+) transients and lipid rafts localization of the receptor. Furthermore, transfection of mGlu1α receptor with mutated caveolin-binding domain reduced localization of the receptor to lipid rafts. Also, application of a peptide blocker of mGlu1α receptor and caveolin binding reduced the Ca(2+) signaling and the lipid rafts localization. CONCLUSIONS: Taken together, these results suggest that the binding of mGlu1α receptor to caveolin is crucial for its lipid rafts localization and mGlu1α receptor-mediated Ca(2+) transients.