Cluster formation of inositol 1,4,5-trisphosphate receptor requires its transition to open state

Yoko Tateishi, Mitsuharu Hattori*, Tomohiro Nakayama, Miwako Iwai, Hiroko Bannai, Takeshi Nakamura, Takayuki Michikawa, Takafumi Inoue, Katsuhiko Mikoshiba

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

71 Citations (Scopus)


The inositol 1,4,5-trisphosphate (IP3) receptor (IP 3R) Ca2+ channel plays pivotal roles in many aspects of physiological and pathological events. It was previously reported that IP 3R forms clusters on the endoplasmic reticulum when cytosolic Ca 2+ concentration ([Ca2+]C) is elevated. However, the molecular mechanism of IP3R clustering remains largely unknown, and thus its physiological significance is far from clear. In this study we found that the time course of clustering of green fluorescent protein-tagged IP3R type 1 (GFP-IP3R1), evoked by IP 3-generating agonists, did not correlate with [Ca2+] C but seemed compatible with cytoplasmic IP3 concentration. IP3 production alone induced GFP-IP 3R1clustering in the absence of a significant increase in [Ca 2+]C but elevated [Ca2+]C without IP3 production did not. Moreover IP3R1 mutants that do not undergo an IP3-induced conformational change failed to form clusters. Thus, IP3R clustering is induced by its IP 3-induced conformational change to the open state. We also found that GFP-IP3R1 clusters colocalized with ERp44, a luminal protein of endoplasmic reticulum that inhibits its channel activity. This is the first example of ligand-induced clustering of a ligand-gated channel protein.

Original languageEnglish
Pages (from-to)6816-6822
Number of pages7
JournalJournal of Biological Chemistry
Issue number8
Publication statusPublished - 2005 Feb 25
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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