A yeast two-hybrid screen identified Filamin-A as a binding partner of the metabotropic glutamate receptor type 7b (mGluR7b) splice variant. In addition, Filamin-A interacted with mGluR4a, mGluR5a, mGluR5b, mGluR7a and mGluR8a. Domain mapping revealed that alternative splicing of mGluR4, mGluR7 and mGluR8 C-termini regulated the interaction. A conserved tyrosine within mGluR C-termini was identified to mediate the binding to Filamin-A. Protein interactions were verified in biochemical assays using recombinant and native proteins. Finally, co-expression of Filamin-A and mGluR7 splice variants was shown in brain regions. These findings suggest that Filamin-A may physically link metabotropic glutamate receptors to the actin cytoskeleton.