IRBIT, an inositol 1,4,5-trisphosphate receptor-binding protein, specifically binds to and activates pancreas-type Na+/HCO 3- cotransporter 1 (pNBC1)

Kyoko Shirakabe, Giuseppina Priori, Hideomi Yamada, Hideaki Ando, Shoko Horita, Toshiro Fujita, Ichiro Fujimoto, Akihiro Mizutani, George Seki, Katsuhiko Mikoshiba

研究成果: Article査読

122 被引用数 (Scopus)

抄録

Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are IP3-gated Ca2+ channels that are located on intracellular Ca2+ stores. We previously identified an IP 3R binding protein, termed IP3R binding protein released with IP3 (IRBIT). Because IRBIT is released from IP3R by physiological concentrations of IP3, we hypothesized that IRBIT is a signaling molecule that is released from IP3R and regulates downstream target molecules in response to the production of IP3. Therefore, in this study, we attempted to identify the target molecules of IRBIT, and we succeeded in identifying Na+/HCO3 - cotransporter 1 (NBC1) as an IRBIT binding protein. Of the two major splicing variants of NBC1, pancreas-type NBC1 (pNBC1) and kidney-type NBC1 (kNBCI), IRBIT was found to bind specifically to pNBC1 and not to bind to kNBC1. IRBIT binds to the N-terminal pNBC1-specific domain, and its binding depends on the phosphorylation of multiple serine residues of IRBIT. Also, an electrophysiological analysis in Xenopus oocytes revealed that pNBC1 requires coexpression of IRBIT to manifest substantial activity comparable with that of kNBC1, which displays substantial activity independently of IRBIT. These results strongly suggest that pNBC1 is the target molecule of IRBIT and that IRBIT has an important role in pH regulation through pNBC1. Also, our findings raise the possibility that the regulation through IRBIT enables NBC1 variants to have different physiological roles.

本文言語English
ページ(範囲)9542-9547
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
103
25
DOI
出版ステータスPublished - 2006 6 20
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ASJC Scopus subject areas

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「IRBIT, an inositol 1,4,5-trisphosphate receptor-binding protein, specifically binds to and activates pancreas-type Na<sup>+</sup>/HCO <sub>3</sub><sup>-</sup> cotransporter 1 (pNBC1)」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

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