Heterodimerization of calcium sensing receptors with metabotropic glutamate receptors in neurons.
Calcium sensing (CaR) and Group I metabotropic glutamate receptors exhibit overlapping expression patterns in brain, and share common signal transduction pathways. To determine whether CaR and Group I metabotropic glutamate receptors (mGluRs) (mGluR1alpha and mGluR5) can form heterodimers, we immunoprecipitated CaR from bovine brain and observed co-precipitation of mGluR1alpha. CaR and mGluR1alpha co-localize in hippocampal and cerebellar neurons, but are expressed separately in other brain regions. In vitro transfection studies in HEK-293 cells established the specificity and disulfide-linked nature of the CaR:mGluR1alpha (CaR:mGluR5) interactions. CaR:mGluR1alpha (CaR:mGluR5) heterodimers exhibit altered trafficking via Homer 1c when compared with CaR:CaR homodimers. CaR becomes sensitive to glutamate-mediated internalization when present in CaR:mGluR1alpha heterodimers. These results demonstrate cross-family covalent heterodimerization of CaR with Group I mGluRs, and increase the potential role(s) for CaR in modulating neuronal function.
Gama
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Department of Physiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA.
Wilt
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Breitwieser
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GE
D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry*; D002417:Cattle; D002460:Cell Line; D002531:Cerebellum / Q000378:metabolism; D019281:Dimerization; D004220:Disulfides; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry*; D014162:Transfection
D002135:Calcium-Binding Proteins; D004220:Disulfides; D018094:Receptors, Metabotropic Glutamate; D002118:Calcium