Cytoskeletal protein 4.1G is a binding partner of the metabotropic glutamate receptor subtype 1 alpha

Recent evidence suggests that cytoskeletal proteins play important roles in the clustering and anchoring of glutamate receptors to the cell surface membrane. To examine further this issue, we tested for direct interactions between the metabotropic glutamate receptor subtype 1alpha (mGlu1alpha) and 4.1G, which is a member of the erythrocyte membrane, cytoskeletal protein 4.1 family. First, co-localization of 4.1G and mGlu1alpha was observed in cultured hippocampal neurons. Second, in transiently transfected HEK 293 cells and in whole rat brain tissue, direct interactions between mGlu1alpha and 4.1G were observed. Third, we were able to identify the C-terminal tail of mGlu1alpha as an essential region for mGlu1alpha-4.1G interactions. Fourth, 4.1 G influences mGlu1alpha-mediated cAMP accumulation. Finally, we found that 4.1G increases the ligand-binding ability of mGlu1alpha and alters its cellular distribution. These observations identify 4.1G as a novel binding partner of mGlu1alpha that can regulate the action of mGlu1alpha.