Splicing variation of Long-IRBIT determines the target selectivity of IRBIT family proteins

Katsuhiro Kawaai, Hideaki Ando, Nobuhiko Satoh, Hideomi Yamada, Naoko Ogawa, Matsumi Hirose, Akihiro Mizutani, Benjamin Bonneau, George Seki, Katsuhiko Mikoshiba

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

IRBIT [inositol 1,4,5-trisphosphate receptor (IP3R) binding protein released with inositol 1,4,5-trisphosphate (IP3)] is a multifunctional protein that regulates several target molecules such as ion channels, transporters, polyadenylation complex, and kinases. Through its interaction with multiple targets, IRBIT contributes to calcium signaling, electrolyte transport, mRNA processing, cell cycle, and neuronal function. However, the regulatory mechanism of IRBIT binding to particular targets is poorly understood. Long-IRBIT is an IRBIT homolog with high homology to IRBIT, except for a unique N-terminal appendage. Long-IRBIT splice variants have different N-terminal sequences and a common C-terminal region, which is involved in multimerization of IRBIT and Long-IRBIT. In this study, we characterized IRBIT and Long-IRBIT splice variants (IRBIT family). We determined that the IRBIT family exhibits different mRNA expression patterns in various tissues. The IRBIT family formed homo- and heteromultimers. In addition, N-terminal splicing of Long-IRBIT changed the protein stability and selectivity to target molecules. These results suggest that N-terminal diversity of the IRBIT family and various combinations of multimer formation contribute to the functional diversity of the IRBIT family.

Original languageEnglish
Pages (from-to)3921-3926
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number15
DOIs
Publication statusPublished - 2017 Apr 11

Keywords

  • IRBIT
  • Long-IRBIT
  • Protein stability
  • Protein–protein interaction
  • Splice variant

ASJC Scopus subject areas

  • General

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