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

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89 Citations (Scopus)

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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