The metabotropic glutamate receptor mGluR7b binds to the catalytic γ‐subunit of protein phosphatase 1

Correct targeting of enzymes represents an important biological mechanism to control post‐translational modifications of neurotransmitter receptors. The metabotropic glutamate receptor type 7 (mGluR7) exists in two splice variants (mGluR7a and mGluR7b), defined by different C‐termini that are phosphorylated by protein kinase C (PKC). Recently, the search for mGluR7a binding partners yielded several proteins that interacted with its C‐terminus. Here, a yeast two‐hybrid screen using the mGluR7b C‐terminus identified both variants of the catalytic γ‐subunit of protein phosphatase 1 (PP1γ1 and PP1γ2) as binding partners. The minimal interacting region of PP1γ1/2 contained the core domain and was homologous to a region of PP1α that is needed for functional expression. Although this core domain is highly conserved within the protein phosphatase family, PP1α1 and PP1β did not interact with mGluR7b. Binding between PP1γ1 and mGluR7b might be regulated by alternative splicing, as the variant‐specific distal part of the mGluR7b C‐terminus mediated the interaction. Within this domain, amino acids involved in the binding to PP1γ1 were mapped and biochemical assays using recombinant and native proteins verified the proposed interaction. Finally, the expression pattern of PP1γ1, PP1γ2 and mGluR7b was analysed in various CNS regions. In summary, these results suggest a regulation of mGluR7b by PP1γ.