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

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

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
Volume280
Issue number8
DOIs
Publication statusPublished - 2005 Feb 25
Externally publishedYes

Fingerprint

Inositol 1,4,5-Trisphosphate Receptors
Green Fluorescent Proteins
Cluster Analysis
Ligand-Gated Ion Channels
Inositol 1,4,5-Trisphosphate
Endoplasmic Reticulum
Proteins
Ligands

ASJC Scopus subject areas

  • Biochemistry

Cite this

Tateishi, Y., Hattori, M., Nakayama, T., Iwai, M., Bannai, H., Nakamura, T., ... Mikoshiba, K. (2005). Cluster formation of inositol 1,4,5-trisphosphate receptor requires its transition to open state. Journal of Biological Chemistry, 280(8), 6816-6822. https://doi.org/10.1074/jbc.M405469200

Cluster formation of inositol 1,4,5-trisphosphate receptor requires its transition to open state. / Tateishi, Yoko; Hattori, Mitsuharu; Nakayama, Tomohiro; Iwai, Miwako; Bannai, Hiroko; Nakamura, Takeshi; Michikawa, Takayuki; Inoue, Takafumi; Mikoshiba, Katsuhiko.

In: Journal of Biological Chemistry, Vol. 280, No. 8, 25.02.2005, p. 6816-6822.

Research output: Contribution to journalArticle

Tateishi, Y, Hattori, M, Nakayama, T, Iwai, M, Bannai, H, Nakamura, T, Michikawa, T, Inoue, T & Mikoshiba, K 2005, 'Cluster formation of inositol 1,4,5-trisphosphate receptor requires its transition to open state', Journal of Biological Chemistry, vol. 280, no. 8, pp. 6816-6822. https://doi.org/10.1074/jbc.M405469200
Tateishi, Yoko ; Hattori, Mitsuharu ; Nakayama, Tomohiro ; Iwai, Miwako ; Bannai, Hiroko ; Nakamura, Takeshi ; Michikawa, Takayuki ; Inoue, Takafumi ; Mikoshiba, Katsuhiko. / Cluster formation of inositol 1,4,5-trisphosphate receptor requires its transition to open state. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 8. pp. 6816-6822.
@article{6cee10ffb8454a8fb641e566b682d5ae,
title = "Cluster formation of inositol 1,4,5-trisphosphate receptor requires its transition to open state",
abstract = "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.",
author = "Yoko Tateishi and Mitsuharu Hattori and Tomohiro Nakayama and Miwako Iwai and Hiroko Bannai and Takeshi Nakamura and Takayuki Michikawa and Takafumi Inoue and Katsuhiko Mikoshiba",
year = "2005",
month = "2",
day = "25",
doi = "10.1074/jbc.M405469200",
language = "English",
volume = "280",
pages = "6816--6822",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "8",

}

TY - JOUR

T1 - Cluster formation of inositol 1,4,5-trisphosphate receptor requires its transition to open state

AU - Tateishi, Yoko

AU - Hattori, Mitsuharu

AU - Nakayama, Tomohiro

AU - Iwai, Miwako

AU - Bannai, Hiroko

AU - Nakamura, Takeshi

AU - Michikawa, Takayuki

AU - Inoue, Takafumi

AU - Mikoshiba, Katsuhiko

PY - 2005/2/25

Y1 - 2005/2/25

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=14844327542&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=14844327542&partnerID=8YFLogxK

U2 - 10.1074/jbc.M405469200

DO - 10.1074/jbc.M405469200

M3 - Article

C2 - 15583010

AN - SCOPUS:14844327542

VL - 280

SP - 6816

EP - 6822

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 8

ER -