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

4 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
Externally publishedYes

Fingerprint

Inositol 1,4,5-Trisphosphate Receptors
Messenger RNA
Polyadenylation
Inositol 1,4,5-Trisphosphate
Calcium Signaling
Protein Stability
Ion Channels
Electrolytes
Cell Cycle
Carrier Proteins
Proteins
Phosphotransferases

Keywords

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

ASJC Scopus subject areas

  • General

Cite this

Splicing variation of Long-IRBIT determines the target selectivity of IRBIT family proteins. / Kawaai, Katsuhiro; Ando, Hideaki; Satoh, Nobuhiko; Yamada, Hideomi; Ogawa, Naoko; Hirose, Matsumi; Mizutani, Akihiro; Bonneau, Benjamin; Seki, George; Mikoshiba, Katsuhiko.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 15, 11.04.2017, p. 3921-3926.

Research output: Contribution to journalArticle

Kawaai, K, Ando, H, Satoh, N, Yamada, H, Ogawa, N, Hirose, M, Mizutani, A, Bonneau, B, Seki, G & Mikoshiba, K 2017, 'Splicing variation of Long-IRBIT determines the target selectivity of IRBIT family proteins', Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 15, pp. 3921-3926. https://doi.org/10.1073/pnas.1618514114
Kawaai, Katsuhiro ; Ando, Hideaki ; Satoh, Nobuhiko ; Yamada, Hideomi ; Ogawa, Naoko ; Hirose, Matsumi ; Mizutani, Akihiro ; Bonneau, Benjamin ; Seki, George ; Mikoshiba, Katsuhiko. / Splicing variation of Long-IRBIT determines the target selectivity of IRBIT family proteins. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 15. pp. 3921-3926.
@article{913159a87d3e4003a9c0102f557c35d0,
title = "Splicing variation of Long-IRBIT determines the target selectivity of IRBIT family proteins",
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.",
keywords = "IRBIT, Long-IRBIT, Protein stability, Protein–protein interaction, Splice variant",
author = "Katsuhiro Kawaai and Hideaki Ando and Nobuhiko Satoh and Hideomi Yamada and Naoko Ogawa and Matsumi Hirose and Akihiro Mizutani and Benjamin Bonneau and George Seki and Katsuhiko Mikoshiba",
year = "2017",
month = "4",
day = "11",
doi = "10.1073/pnas.1618514114",
language = "English",
volume = "114",
pages = "3921--3926",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "15",

}

TY - JOUR

T1 - Splicing variation of Long-IRBIT determines the target selectivity of IRBIT family proteins

AU - Kawaai, Katsuhiro

AU - Ando, Hideaki

AU - Satoh, Nobuhiko

AU - Yamada, Hideomi

AU - Ogawa, Naoko

AU - Hirose, Matsumi

AU - Mizutani, Akihiro

AU - Bonneau, Benjamin

AU - Seki, George

AU - Mikoshiba, Katsuhiko

PY - 2017/4/11

Y1 - 2017/4/11

N2 - 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.

AB - 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.

KW - IRBIT

KW - Long-IRBIT

KW - Protein stability

KW - Protein–protein interaction

KW - Splice variant

UR - http://www.scopus.com/inward/record.url?scp=85035234927&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85035234927&partnerID=8YFLogxK

U2 - 10.1073/pnas.1618514114

DO - 10.1073/pnas.1618514114

M3 - Article

C2 - 28348216

AN - SCOPUS:85035234927

VL - 114

SP - 3921

EP - 3926

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 15

ER -