The metabotropic glutamate receptor mGluR7b binds to the catalytic gamma-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 gamma-subunit of protein phosphatase 1 (PP1gamma1 and PP1gamma2) as binding partners. The minimal interacting region of PP1gamma1/2 contained the core domain and was homologous to a region of PP1alpha that is needed for functional expression. Although this core domain is highly conserved within the protein phosphatase family, PP1alpha1 and PP1beta did not interact with mGluR7b. Binding between PP1gamma1 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 PP1gamma1 were mapped and biochemical assays using recombinant and native proteins verified the proposed interaction. Finally, the expression pattern of PP1gamma1, PP1gamma2 and mGluR7b was analysed in various CNS regions. In summary, these results suggest a regulation of mGluR7b by PP1gamma.
Enz
Ralf
R
Emil-Fischer Zentrum, Institut für Biochemie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany. ralf.enz@biochem.uni-erlangen.de
D017398:Alternative Splicing / Q000502:physiology; D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D020134:Catalytic Domain / Q000502:physiology; D002490:Central Nervous System / Q000378:metabolism; D003598:Cytoskeletal Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D054645:Protein Phosphatase 1; D017434:Protein Structure, Tertiary / Q000502:physiology; D021122:Protein Subunits; D012313:RNA / Q000378:metabolism; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D009687:Nuclear Proteins; C498298:PICK1 protein, rat; D010446:Peptide Fragments; D020033:Protein Isoforms; D021122:Protein Subunits; D018094:Receptors, Metabotropic Glutamate; D011994:Recombinant Proteins; C102719:metabotropic glutamate receptor 7; D012313:RNA; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1