Heterodimerization of Calcium Sensing Receptors with Metabotropic Glutamate Receptors in Neurons

Lucio Gama, Susan G. Wilt, Gerda E. Breitwieser

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)39053-39059
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number42
DOIs
StatePublished - Oct 19 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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