AHCYL2 (long-IRBIT) as a potential regulator of the electrogenic Na-HCO3 cotransporter NBCe1-B

Although AHCYL2 (long-IRBIT) is highly homologous to IRBIT, which regulates ion-transporting proteins including the electrogenic Na⁺-HCO₃⁻ cotransporter NBCe1-B, its functions are poorly understood. Here, we found that AHCYL2 interacts with NBCe1-B in bovine parotid acinar cells using yeast two-hybrid, immunofluorescence confocal microscopy and co-immunoprecipitation analyses. Whole-cell patch-clamp experiments revealed that co-expression of AHCYL2 reduces the apparent affinity for intracellular Mg²⁺ in inhibition of NBCe1-B currents specifically in a HCO₃⁻-deficient cellular condition. Our data unveil AHCYL2 as a potential regulator of NBCe1-B in mammalian cells. We propose that cytosolic ionic condition appropriate for AHCYL2 to function might be different from IRBIT.