Distinct Roles of Inositol 1,4,5-Trisphosphate Receptor Types 1 and 3 in Ca2+ Signaling

Mitsuharu Hattori, Akinobu Z. Suzuki, Takayasu Higo, Hiroshi Miyauchi, Takayuki Michikawa, Takeshi Nakamura, Takafumi Inoue, Katsuhiko Mikoshiba

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Three subtypes of inositol 1,4,5-trisphosphate receptor (IP3R1, IP3R2, and IP3R3) Ca2+ release channel share basic properties but differ in terms of regulation. To what extent they contribute to complex Ca2+ signaling, such as Ca2+ oscillations, remains largely unknown. Here we show that HeLa cells express comparable amounts of IP3R1 and IP3R3, but knockdown by RNA interference of each subtype results in dramatically distinct Ca 2+ signaling patterns. Knockdown of IP3R1 significantly decreases total Ca2+ signals and terminates Ca2+ oscillations. Conversely, knockdown of IP3R3 leads to more robust and long lasting Ca2+ oscillations than in controls. Effects of IP3R3 knockdown are surprisingly similar in COS-7 cells that predominantly (>90% of total IP3R) express IP3R3, suggesting that IP3R3 functions as an anti-Ca 2+-oscillatory unit without contributing to peak amplitude of Ca 2+ signals, irrespective of its relative expression level. Therefore, differential expression of the IP3R subtype is critical for various forms of Ca2+ signaling, and, particularly, IP3R1 and IP3R3 have opposite roles in generating Ca2+ oscillations.

Original languageEnglish
Pages (from-to)11967-11975
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number12
DOIs
Publication statusPublished - 2004 Mar 19
Externally publishedYes

Fingerprint

Inositol 1,4,5-Trisphosphate Receptors
COS Cells
RNA Interference
HeLa Cells
RNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

Hattori, M., Suzuki, A. Z., Higo, T., Miyauchi, H., Michikawa, T., Nakamura, T., ... Mikoshiba, K. (2004). Distinct Roles of Inositol 1,4,5-Trisphosphate Receptor Types 1 and 3 in Ca2+ Signaling. Journal of Biological Chemistry, 279(12), 11967-11975. https://doi.org/10.1074/jbc.M311456200

Distinct Roles of Inositol 1,4,5-Trisphosphate Receptor Types 1 and 3 in Ca2+ Signaling. / Hattori, Mitsuharu; Suzuki, Akinobu Z.; Higo, Takayasu; Miyauchi, Hiroshi; Michikawa, Takayuki; Nakamura, Takeshi; Inoue, Takafumi; Mikoshiba, Katsuhiko.

In: Journal of Biological Chemistry, Vol. 279, No. 12, 19.03.2004, p. 11967-11975.

Research output: Contribution to journalArticle

Hattori, M, Suzuki, AZ, Higo, T, Miyauchi, H, Michikawa, T, Nakamura, T, Inoue, T & Mikoshiba, K 2004, 'Distinct Roles of Inositol 1,4,5-Trisphosphate Receptor Types 1 and 3 in Ca2+ Signaling', Journal of Biological Chemistry, vol. 279, no. 12, pp. 11967-11975. https://doi.org/10.1074/jbc.M311456200
Hattori M, Suzuki AZ, Higo T, Miyauchi H, Michikawa T, Nakamura T et al. Distinct Roles of Inositol 1,4,5-Trisphosphate Receptor Types 1 and 3 in Ca2+ Signaling. Journal of Biological Chemistry. 2004 Mar 19;279(12):11967-11975. https://doi.org/10.1074/jbc.M311456200
Hattori, Mitsuharu ; Suzuki, Akinobu Z. ; Higo, Takayasu ; Miyauchi, Hiroshi ; Michikawa, Takayuki ; Nakamura, Takeshi ; Inoue, Takafumi ; Mikoshiba, Katsuhiko. / Distinct Roles of Inositol 1,4,5-Trisphosphate Receptor Types 1 and 3 in Ca2+ Signaling. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 12. pp. 11967-11975.
@article{58347f7955624f10a657889b5cdd90ed,
title = "Distinct Roles of Inositol 1,4,5-Trisphosphate Receptor Types 1 and 3 in Ca2+ Signaling",
abstract = "Three subtypes of inositol 1,4,5-trisphosphate receptor (IP3R1, IP3R2, and IP3R3) Ca2+ release channel share basic properties but differ in terms of regulation. To what extent they contribute to complex Ca2+ signaling, such as Ca2+ oscillations, remains largely unknown. Here we show that HeLa cells express comparable amounts of IP3R1 and IP3R3, but knockdown by RNA interference of each subtype results in dramatically distinct Ca 2+ signaling patterns. Knockdown of IP3R1 significantly decreases total Ca2+ signals and terminates Ca2+ oscillations. Conversely, knockdown of IP3R3 leads to more robust and long lasting Ca2+ oscillations than in controls. Effects of IP3R3 knockdown are surprisingly similar in COS-7 cells that predominantly (>90{\%} of total IP3R) express IP3R3, suggesting that IP3R3 functions as an anti-Ca 2+-oscillatory unit without contributing to peak amplitude of Ca 2+ signals, irrespective of its relative expression level. Therefore, differential expression of the IP3R subtype is critical for various forms of Ca2+ signaling, and, particularly, IP3R1 and IP3R3 have opposite roles in generating Ca2+ oscillations.",
author = "Mitsuharu Hattori and Suzuki, {Akinobu Z.} and Takayasu Higo and Hiroshi Miyauchi and Takayuki Michikawa and Takeshi Nakamura and Takafumi Inoue and Katsuhiko Mikoshiba",
year = "2004",
month = "3",
day = "19",
doi = "10.1074/jbc.M311456200",
language = "English",
volume = "279",
pages = "11967--11975",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "12",

}

TY - JOUR

T1 - Distinct Roles of Inositol 1,4,5-Trisphosphate Receptor Types 1 and 3 in Ca2+ Signaling

AU - Hattori, Mitsuharu

AU - Suzuki, Akinobu Z.

AU - Higo, Takayasu

AU - Miyauchi, Hiroshi

AU - Michikawa, Takayuki

AU - Nakamura, Takeshi

AU - Inoue, Takafumi

AU - Mikoshiba, Katsuhiko

PY - 2004/3/19

Y1 - 2004/3/19

N2 - Three subtypes of inositol 1,4,5-trisphosphate receptor (IP3R1, IP3R2, and IP3R3) Ca2+ release channel share basic properties but differ in terms of regulation. To what extent they contribute to complex Ca2+ signaling, such as Ca2+ oscillations, remains largely unknown. Here we show that HeLa cells express comparable amounts of IP3R1 and IP3R3, but knockdown by RNA interference of each subtype results in dramatically distinct Ca 2+ signaling patterns. Knockdown of IP3R1 significantly decreases total Ca2+ signals and terminates Ca2+ oscillations. Conversely, knockdown of IP3R3 leads to more robust and long lasting Ca2+ oscillations than in controls. Effects of IP3R3 knockdown are surprisingly similar in COS-7 cells that predominantly (>90% of total IP3R) express IP3R3, suggesting that IP3R3 functions as an anti-Ca 2+-oscillatory unit without contributing to peak amplitude of Ca 2+ signals, irrespective of its relative expression level. Therefore, differential expression of the IP3R subtype is critical for various forms of Ca2+ signaling, and, particularly, IP3R1 and IP3R3 have opposite roles in generating Ca2+ oscillations.

AB - Three subtypes of inositol 1,4,5-trisphosphate receptor (IP3R1, IP3R2, and IP3R3) Ca2+ release channel share basic properties but differ in terms of regulation. To what extent they contribute to complex Ca2+ signaling, such as Ca2+ oscillations, remains largely unknown. Here we show that HeLa cells express comparable amounts of IP3R1 and IP3R3, but knockdown by RNA interference of each subtype results in dramatically distinct Ca 2+ signaling patterns. Knockdown of IP3R1 significantly decreases total Ca2+ signals and terminates Ca2+ oscillations. Conversely, knockdown of IP3R3 leads to more robust and long lasting Ca2+ oscillations than in controls. Effects of IP3R3 knockdown are surprisingly similar in COS-7 cells that predominantly (>90% of total IP3R) express IP3R3, suggesting that IP3R3 functions as an anti-Ca 2+-oscillatory unit without contributing to peak amplitude of Ca 2+ signals, irrespective of its relative expression level. Therefore, differential expression of the IP3R subtype is critical for various forms of Ca2+ signaling, and, particularly, IP3R1 and IP3R3 have opposite roles in generating Ca2+ oscillations.

UR - http://www.scopus.com/inward/record.url?scp=1642523571&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1642523571&partnerID=8YFLogxK

U2 - 10.1074/jbc.M311456200

DO - 10.1074/jbc.M311456200

M3 - Article

C2 - 14707143

AN - SCOPUS:1642523571

VL - 279

SP - 11967

EP - 11975

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 12

ER -