IRBIT: A regulator of ion channels and ion transporters

• Published in: Biochimica et biophysica acta 2014-10, Vol.1843 (10), p.2195-2204
• Main Authors: Ando, Hideaki, Kawaai, Katsuhiro, Mikoshiba, Katsuhiko
• Format: Article
• Language: English
• Subjects: Cl− channel, CFTR; Cl−/HCO3− exchanger, Slc26a6; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; Eukaryotic Cells - cytology; Eukaryotic Cells - metabolism; Evolution, Molecular; Gene Expression Regulation; Humans; Inositol 1,4,5-Trisphosphate Receptors - genetics; Inositol 1,4,5-Trisphosphate Receptors - metabolism; Ion Channel Gating; IP3 receptor; IRBIT; Lectins, C-Type - genetics; Lectins, C-Type - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; Na+/H+ exchanger, NHE3; Na+/HCO3− co-transporter, NBCe1-B; Protein Structure, Secondary; Protein Structure, Tertiary; Signal Transduction; Sodium-Bicarbonate Symporters - genetics; Sodium-Bicarbonate Symporters - metabolism; Sodium-Hydrogen Exchanger 3; Sodium-Hydrogen Exchangers - genetics; Sodium-Hydrogen Exchangers - metabolism
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/j.bbamcr.2014.01.031

IRBIT (also called AHCYL1) was originally identified as a binding protein of the intracellular Ca2+ channel inositol 1,4,5-trisphosphate (IP3) receptor and functions as an inhibitory regulator of this receptor. Unexpectedly, many functions have subsequently been identified for IRBIT including the activation of multiple ion channels and ion transporters, such as the Na+/HCO3− co-transporter NBCe1-B, the Na+/H+ exchanger NHE3, the Cl− channel cystic fibrosis transmembrane conductance regulator (CFTR), and the Cl−/HCO3− exchanger Slc26a6. The characteristic serine-rich region in IRBIT plays a critical role in the functions of this protein. In this review, we describe the evolution, domain structure, expression pattern, and physiological roles of IRBIT and discuss the potential molecular mechanisms underlying the coordinated regulation of these diverse ion channels/transporters through IRBIT. This article is part of a Special Issue entitled: Calcium signaling in health and disease. Guest Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and Marc Moreau. •IRBIT suppresses IP3 receptor at resting state.•IRBIT activates ion transporters/channels including NBCe1-B, NHE3, CFTR, and Slc26a6.•The activity of IRBIT is regulated by phosphorylation in the serine-rich region.•IRBIT coordinates epithelial fluid and HCO3− secretion.