Fig. 3.

IRBIT coordinates pancreatic duct fluid and HCO₃⁻ secretion. The model shows the key transporters involved in pancreatic duct fluid and HCO₃⁻ salvage and secretion. In the resting state, IRBIT forms complexes with the luminal NHE3 and NBCn1 to salvage leaked fluid and HCO₃⁻. Cell stimulation results in formation of complexes between IRBIT and the basolateral NBCe1-B and the luminal CFTR that are assembled by PDZ domains-containing scaffolding proteins. The interaction is mediated by the IRBIT PEST domain (red circles) and requires the IRBIT coiled-coil domain (green circles). In the case of CFTR, an additional unknown protein (marked as protein X) is needed for activation of CFTR by IRBIT. Activation of NBCe1-B and CFTR by IRBIT coordinates HCO₃⁻ entry at the basolateral membrane and HCO₃⁻ exit at the luminal membrane to ensure the fidelity of epithelial fluid and HCO₃⁻ secretion