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.
Mesh Terms:
Animals, Brain, Calcium, Calcium-Binding Proteins, Cattle, Cell Line, Cerebellum, Dimerization, Disulfides, Enzyme-Linked Immunosorbent Assay, Hippocampus, Humans, Microscopy, Fluorescence, Neurons, Precipitin Tests, Protein Binding, Rats, Receptors, Metabotropic Glutamate, Transfection
Animals, Brain, Calcium, Calcium-Binding Proteins, Cattle, Cell Line, Cerebellum, Dimerization, Disulfides, Enzyme-Linked Immunosorbent Assay, Hippocampus, Humans, Microscopy, Fluorescence, Neurons, Precipitin Tests, Protein Binding, Rats, Receptors, Metabotropic Glutamate, Transfection
J. Biol. Chem.
Date: Oct. 19, 2001
PubMed ID: 11489900
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