Molecular cloning of mouse type 2 and type 3 inositol 1,4,5-trisphosphate receptors and identification of a novel type 2 receptor splice variant

Miwako Iwai, Yoko Tateishi, Mitsuharu Hattori, Akihiro Mizutani, Takeshi Nakamura, Akira Futatsugi, Takafumi Inoue, Teiichi Furuichi, Takayuki Michikawa, Katsuhiko Mikoshiba

Research output: Contribution to journalArticle

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Abstract

We isolated cDNAs encoding type 2 and type 3 inositol 1,4,5-trisphosphate (IP3) receptors (IP3R2 and IP3R3, respectively) from mouse lung and found a novel alternative splicing segment, SI m2, at 176-208 of IP3R2. The long form (IP3R2 SIm2 +) was dominant, but the short form (IP3R2 SIm2 -) was detected in all tissues examined. IP 3R2 SIm2 - has neither IP3 binding activity nor Ca2+ releasing activity. In addition to its reticular distribution, IP3R2 SIm2 + is present in the form of clusters in the endoplasmic reticulum of resting COS-7 cells, and after ATP or Ca2+ ionophore stimulation, most of the IP3R2 SIm2 + is in clusters. IP3R3 is localized uniformly on the endoplasmic reticulum of resting cells and forms clusters after ATP or Ca2+ ionophore stimulation. IP3R2 SI m2 - does not form clusters in either resting or stimulated cells. IP3 binding-deficient site-directed mutants of IP 3R2 SIm2 + and IP3R3 fail to form clusters, indicating that IP3 binding is involved in the cluster formation by these isoforms. Coespression of IP3R2 SI m2 - prevents stimulus-induced IP3R clustering, suggesting that IP3R2 SIm2 - functions as a negative coordinator of stimulusinduced IP3R clustering. Expression of IP3R2 SIm2 - in CHO-K1 cells significantly reduced ATP-induced Ca2+ entry, but not Ca2+ release, suggesting that the novel splice variant of IP3R2 specifically influences the dynamics of the sustained phase of Ca2+ signals.

Original languageEnglish
Pages (from-to)10305-10317
Number of pages13
JournalJournal of Biological Chemistry
Volume280
Issue number11
DOIs
Publication statusPublished - 2005 Mar 18
Externally publishedYes

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Inositol 1,4,5-Trisphosphate Receptors
Cloning
Molecular Cloning
Adenosine Triphosphate
Ionophores
Endoplasmic Reticulum
Cluster Analysis
Inositol 1,4,5-Trisphosphate
CHO Cells
COS Cells
Alternative Splicing
Binding sites
Protein Isoforms
Complementary DNA
Binding Sites
Tissue
Lung
Mouse Ip3r2 protein

ASJC Scopus subject areas

  • Biochemistry

Cite this

Molecular cloning of mouse type 2 and type 3 inositol 1,4,5-trisphosphate receptors and identification of a novel type 2 receptor splice variant. / Iwai, Miwako; Tateishi, Yoko; Hattori, Mitsuharu; Mizutani, Akihiro; Nakamura, Takeshi; Futatsugi, Akira; Inoue, Takafumi; Furuichi, Teiichi; Michikawa, Takayuki; Mikoshiba, Katsuhiko.

In: Journal of Biological Chemistry, Vol. 280, No. 11, 18.03.2005, p. 10305-10317.

Research output: Contribution to journalArticle

Iwai, M, Tateishi, Y, Hattori, M, Mizutani, A, Nakamura, T, Futatsugi, A, Inoue, T, Furuichi, T, Michikawa, T & Mikoshiba, K 2005, 'Molecular cloning of mouse type 2 and type 3 inositol 1,4,5-trisphosphate receptors and identification of a novel type 2 receptor splice variant', Journal of Biological Chemistry, vol. 280, no. 11, pp. 10305-10317. https://doi.org/10.1074/jbc.M413824200
Iwai, Miwako ; Tateishi, Yoko ; Hattori, Mitsuharu ; Mizutani, Akihiro ; Nakamura, Takeshi ; Futatsugi, Akira ; Inoue, Takafumi ; Furuichi, Teiichi ; Michikawa, Takayuki ; Mikoshiba, Katsuhiko. / Molecular cloning of mouse type 2 and type 3 inositol 1,4,5-trisphosphate receptors and identification of a novel type 2 receptor splice variant. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 11. pp. 10305-10317.
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AU - Nakamura, Takeshi

AU - Futatsugi, Akira

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