Abstract P2038: A Nobel I551F Mutant of Sodium Handling Transporter NBCe1 Has Cytosolic Retention and Diminishes Transport Activity

The electrogenic Na + /HCO 3 - cotransporter NBCe1 is expressed in many organs and controls sodium handling. NBCe1 homozygous mutation causes not only severe hypotension but also proximal renal tubular acidosis in human and rodents. Here we shows the functional significance of the mutations reported from NCBI database on NBCe1 function. We identified 14 mutations in NBCe1 variant A(kidney type), resulting in the single amino acid substitutions, A425T, F461L, A465S, L494F, N503H, A518T, A518G, I523V, V533D, Y535H, I551F, Y554H, M753V, and L785I. Immunocytological analysis with confocal microscopy revealed only I551F mutant was expressed predominantly in the cytoplasm of HEK 293 cells and MDCK cells. Functional analysis using Xenopus oocytes revealed that I551F mutant had a significantly reduced activity corresponding to 52% of that of wild-type (p