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.
authors.affiliation: Laboratory for Developmental Neurobiology, Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Kawaai
authors.affiliation: Laboratory for Developmental Neurobiology, Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ando
authors.affiliation: Department of Internal Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Satoh
authors.affiliation: Department of Internal Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Hideomi
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Laboratory for Developmental Neurobiology, Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Ogawa
authors.affiliation: Laboratory for Developmental Neurobiology, Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan.
authors.forename: Matsumi
authors.initials: M
authors.lastname: Hirose
authors.affiliation: Department of Pharmacotherapeutics, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Mizutani
authors.affiliation: Laboratory for Developmental Neurobiology, Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bonneau
authors.affiliation: Department of Internal Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: George
authors.initials: G
authors.lastname: Seki
authors.affiliation: Laboratory for Developmental Neurobiology, Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan; mikosiba@brain.riken.jp.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
mesh_terms: D043383:Adenosylhomocysteinase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D020013:Calcium Signaling; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002522:Chlorocebus aethiops; D005260:Female; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D020033:Protein Isoforms; D055550:Protein Stability; D027982:Sodium-Bicarbonate Symporters / Q000235:genetics / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3 / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: C470184:CLECL1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D037181:Lectins, C-Type; D008565:Membrane Proteins; D020033:Protein Isoforms; C498899:Slc4a4 protein, mouse; C000613386:Slc9a3 protein, mouse; D027982:Sodium-Bicarbonate Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D043383:Adenosylhomocysteinase; C510392:IRBIT protein, mouse
keywords: IRBIT; Long-IRBIT; protein stability; protein–protein interaction; splice variant