Juliano Z. Polidoro, Nádia Osório de Oliveira, Erika F. Jesus, Nilberto Robson Falcão do Nascimento, Cláudia Ferreira Santos, Adriana C. C. Girardi
This study reveals that NHE3, SGLT2, and their accessory proteins, PDZK1 and MAP17, assemble into a multiprotein complex in the renal proximal tubule. The merged NHE3-SGLT2 signals show distinct intensity in females, suggesting potential sex-specific differences in complex composition or organization. Acute empagliflozin infusion modifies the colocalization patterns of NHE3 with SGLT2 and MAP17 without disrupting complex integrity, supporting a model in which SGLT2 inhibitors regulate NHE3 through conformational rearrangements within this native complex.