Ca2+-sensor region of IP3 receptor controls intracellular Ca2+ signaling

Tomoya Miyakawa, Akiko Mizushima, Kenzo Hirose, Toshiko Yamazawa, Ilya Bezprozvanny, Tomohiro Kurosaki, Masamitsu Iino

Research output: Contribution to journalArticlepeer-review

120 Scopus citations


Many important cell functions are controlled by Ca2+ release from intracellular stores via the inositol 1,4,5-trisphosphate receptor (IP3R), which requires both IP3 and Ca2+ for its activity. Due to the Ca2+ requirement, the IP3R and the cytoplasmic Ca2+ concentration form a positive feedback loop, which has been assumed to confer regenerativity on the IP3-induced Ca2+ release and to play an important role in the generation of spatiotemporal patterns of Ca2+ signals such as Ca2+ waves and oscillations. Here we show that glutamate 2100 of rat type 1 IP3R (IP3R1) is a key residue for the Ca2+ requirement. Substitution of this residue by aspartate (E2100D) results in a 10-fold decrease in the Ca2+ sensitivity without other effects on the properties of the IP3R1. Agonist-induced Ca2+ responses are greatly diminished in cells expressing the E2100D mutant IP3R1, particularly the rate of rise of initial Ca2+ spike is markedly reduced and the subsequent Ca2+ oscillations are abolished. These results demonstrate that the Ca2+ sensitivity of the IP3R is functionally indispensable for the determination of Ca2+ signaling patterns.

Original languageEnglish (US)
Pages (from-to)1674-1680
Number of pages7
JournalEMBO Journal
Issue number7
StatePublished - Apr 2 2001


  • Calcium
  • Calcium signaling
  • IP receptor
  • Inositol 1,4,5-trisphosphate
  • Point mutation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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