TY - JOUR
T1 - Heterodimerization of Calcium Sensing Receptors with Metabotropic Glutamate Receptors in Neurons
AU - Gama, Lucio
AU - Wilt, Susan G.
AU - Breitwieser, Gerda E.
PY - 2001/10/19
Y1 - 2001/10/19
N2 - 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) (mGluR1α and mGluR5) can form heterodimers, we immunoprecipitated CaR from bovine brain and observed co-precipitation of mGluR1α. CaR and mGluR1α 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:mGluR1α (CaR: mGluR5) interactions. CaR:mGluR1α (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:mGluR1α 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.
AB - 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) (mGluR1α and mGluR5) can form heterodimers, we immunoprecipitated CaR from bovine brain and observed co-precipitation of mGluR1α. CaR and mGluR1α 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:mGluR1α (CaR: mGluR5) interactions. CaR:mGluR1α (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:mGluR1α 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.
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U2 - 10.1074/jbc.M105662200
DO - 10.1074/jbc.M105662200
M3 - Article
C2 - 11489900
AN - SCOPUS:0035914405
SN - 0021-9258
VL - 276
SP - 39053
EP - 39059
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 42
ER -