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

ABSTRACT:

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? 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-?-cyclodextrin markedly decreased mGlu1? receptor-mediated Ca2+ transients and lipid rafts localization of the receptor. Furthermore, transfection of mGlu1? receptor with mutated caveolin-binding domain reduced localization of the receptor to lipid rafts. Also, application of a peptide blocker of mGlu1? receptor and caveolin binding reduced the Ca2+ signaling and the lipid rafts localization.

Conclusions

Taken together, these results suggest that the binding of mGlu1? receptor to caveolin is crucial for its lipid rafts localization and mGlu1? receptor-mediated Ca2+ transients.

SUBMITTER: Roh SE 

PROVIDER: S-EPMC3937055 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature