A group II metabotropic glutamate receptor 3 (mGlu3, GRM3) isoform implicated in schizophrenia interacts with canonical mGlu3 and reduces ligand binding

作者：Garcia Bea Aintzane; Bermudez Isabel; Harrison Paul J^*; Lane Tracy A

来源：Journal of Psychopharmacology, 2017, 31(12): 1519-1526.

DOI：10.1177/0269881117715597

• Metabotropic glutamate receptor
• alternative splicing
• G protein-coupled receptor
• isoform
• schizophrenia

As well as being expressed as a full-length transcript, the group II metabotropic glutamate receptor 3 (GRM3, mGlu3) gene is expressed as an mRNA isoform which lacks exon 4 (GRM34) and which is predicted to encode a protein with a novel C terminus (called mGlu34). This variant may contribute to the mechanism by which GRM3 acts as a schizophrenia risk gene. However, little is known about the properties or function of mGlu34. Here, using transiently transfected HEK293T/17 cells, we confirm that GRM34 cDNA is translated, with mGlu34 existing as a homodimer as well as a monomer, and localizing primarily to cell membranes including the plasma membrane. Co-immunoprecipitation shows that mGlu34 interacts with canonical mGlu3. mGlu34 does not bind the mGlu2/3 antagonist [H-3]LY341495, but the presence of mGlu34 reduces binding of [H-3]LY341495 to mGlu3, paralleled by a decrease in the abundance of membrane-associated mGlu3. These experiments indicate that mGlu34 may negatively modulate mGlu3, and thereby impact on the roles of GRM3/mGlu3 in schizophrenia and as a therapeutic target.

• 出版日期2017-12