A group II metabotropic glutamate receptor 3 (mGlu3, GRM3) isoform implicated in schizophrenia interacts with canonical mGlu3 and reduces ligand binding
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 (GRM3Δ4) and which is predicted to encode a protein with a novel C terminus (called mGlu3 ∆4). This variant may contribute to t...
| Main Authors: | , , , |
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| Format: | Journal article |
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SAGE Publications
2017
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| _version_ | 1797102936631803904 |
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| author | Garcia-Bea, A Bermudez, I Harrison, P Lane, T |
| author_facet | Garcia-Bea, A Bermudez, I Harrison, P Lane, T |
| author_sort | Garcia-Bea, A |
| collection | OXFORD |
| description | 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 (GRM3Δ4) and which is predicted to encode a protein with a novel C terminus (called mGlu3 ∆4). 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 mGlu3 ∆4. Here, using transiently transfected HEK293T/17 cells, we confirm that GRM3Δ4 cDNA is translated, with mGlu3 ∆4 existing as a homodimer as well as a monomer, and localising primarily to cell membranes including the plasma membrane. Coimmunoprecipitation shows that mGlu3∆4 interacts with canonical mGlu3. mGlu3∆4 does not bind the mGlu2/3 antagonist [<sup>3</sup>H]LY341495, but the presence of mGlu3 ∆4 reduces binding of [ <sup>3</sup>H]LY341495 to mGlu3, paralleled by a decrease in the abundance of membrane-associated mGlu3. These experiments indicate that mGlu3 ∆4 may negatively modulate mGlu3, and thereby impact on the roles of GRM3/mGlu3 in schizophrenia and as a therapeutic target. |
| first_indexed | 2024-03-07T06:12:55Z |
| format | Journal article |
| id | oxford-uuid:f0222e5a-f192-47d1-a064-f1d635de5600 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T06:12:55Z |
| publishDate | 2017 |
| publisher | SAGE Publications |
| record_format | dspace |
| spelling | oxford-uuid:f0222e5a-f192-47d1-a064-f1d635de56002022-03-27T11:45:29ZA group II metabotropic glutamate receptor 3 (mGlu3, GRM3) isoform implicated in schizophrenia interacts with canonical mGlu3 and reduces ligand bindingJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f0222e5a-f192-47d1-a064-f1d635de5600Symplectic Elements at OxfordSAGE Publications2017Garcia-Bea, ABermudez, IHarrison, PLane, TAs 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 (GRM3Δ4) and which is predicted to encode a protein with a novel C terminus (called mGlu3 ∆4). 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 mGlu3 ∆4. Here, using transiently transfected HEK293T/17 cells, we confirm that GRM3Δ4 cDNA is translated, with mGlu3 ∆4 existing as a homodimer as well as a monomer, and localising primarily to cell membranes including the plasma membrane. Coimmunoprecipitation shows that mGlu3∆4 interacts with canonical mGlu3. mGlu3∆4 does not bind the mGlu2/3 antagonist [<sup>3</sup>H]LY341495, but the presence of mGlu3 ∆4 reduces binding of [ <sup>3</sup>H]LY341495 to mGlu3, paralleled by a decrease in the abundance of membrane-associated mGlu3. These experiments indicate that mGlu3 ∆4 may negatively modulate mGlu3, and thereby impact on the roles of GRM3/mGlu3 in schizophrenia and as a therapeutic target. |
| spellingShingle | Garcia-Bea, A Bermudez, I Harrison, P Lane, T A group II metabotropic glutamate receptor 3 (mGlu3, GRM3) isoform implicated in schizophrenia interacts with canonical mGlu3 and reduces ligand binding |
| title | A group II metabotropic glutamate receptor 3 (mGlu3, GRM3) isoform implicated in schizophrenia interacts with canonical mGlu3 and reduces ligand binding |
| title_full | A group II metabotropic glutamate receptor 3 (mGlu3, GRM3) isoform implicated in schizophrenia interacts with canonical mGlu3 and reduces ligand binding |
| title_fullStr | A group II metabotropic glutamate receptor 3 (mGlu3, GRM3) isoform implicated in schizophrenia interacts with canonical mGlu3 and reduces ligand binding |
| title_full_unstemmed | A group II metabotropic glutamate receptor 3 (mGlu3, GRM3) isoform implicated in schizophrenia interacts with canonical mGlu3 and reduces ligand binding |
| title_short | A group II metabotropic glutamate receptor 3 (mGlu3, GRM3) isoform implicated in schizophrenia interacts with canonical mGlu3 and reduces ligand binding |
| title_sort | group ii metabotropic glutamate receptor 3 mglu3 grm3 isoform implicated in schizophrenia interacts with canonical mglu3 and reduces ligand binding |
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