Direct Interaction and Functional Coupling between Metabotropic Glutamate Receptor Subtype 1 and Voltage-sensitive Cav2.1 Ca2+ Channel

Jun Kitano, Motohiro Nishida, Yuko Itsukaichi, Itsunari Minami, Masaaki Ogawa, Tomoo Hirano, Yasuo Mori, Shigetada Nakanishi

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Intracellular Ca2+ concentrations ([Ca2+] i) are regulated in a spatiotemporal manner via both entry of extracellular Ca2+ and mobilization of Ca2+ from intracellular stores. Metabotropic glutamate receptor subtype 1 (mGluR1) is a G protein-coupled receptor that stimulates the inositol 1,4,5-trisphosphate-Ca2+ signaling cascade, whereas Cav2. 1 is a pore-forming channel protein of P/Q-type voltage-sensitive Ca 2+ channels. In this investigation, we showed that mGluR1 and Ca v2.1 are colocalized at dendrites of cerebellar Purkinje neurons and form the heteromeric assembly in both the brain and heterologously expressing COS-7 cells. This assembly occurs through the direct interaction between their carboxyl-terminal intracellular domains. Calcium imaging and whole-cell recording showed that mGluR1 inhibits Cav2.1-mediated [Ca 2+]i increases and Ba2+ currents in HEK 293 cells expressing Cav2.1 with auxiliary α2/δ and β1 subunits, respectively. This inhibition occurred in a ligand-independent manner and was enhanced by pre-activation of mGluR1 in a ligand-dependent manner. In contrast, simultaneous stimulation of mGluR1 and Cav2.1 induced large [Ca2+]i increases. Furthermore, the temporally regulated inhibition and stimulation of [Ca2+]i increases by mGluR1 and Cav2.1 were observed at dendrites but not soma of cultured Purkinje neurons. These data suggest that the assembly of mGluR1 and Cav2.1 provides the mechanism that ensures spatiotemporal regulation of [Ca2+]i in glutamatergic neurotransmission.

Original languageEnglish
Pages (from-to)25101-25108
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number27
DOIs
Publication statusPublished - Jul 4 2003

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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