The intracellular lipid-binding domain of human Na/H exchanger 1 forms a lipid-protein co-structure essential for activity.

Dynamic interactions of proteins with lipid membranes are essential regulatory events in biology, but remain rudimentarily understood and particularly overlooked in membrane proteins. The ubiquitously expressed membrane protein Na/H-exchanger 1 (NHE1) regulates intracellular pH (pH) with dysregulation linked to e.g.

Trafficking, localization and degradation of the Na,HCO co-transporter NBCn1 in kidney and breast epithelial cells.

The Na+;HCO3 co-transporter NBCn1 (SLC4A7) is a major regulator of intracellular pH yet its trafficking and turnover are essentially unstudied. Here, we used MDCK-II and MCF-7 cells to investigate these processes in epithelial cells. GFP-NBCn1 membrane localization was abolished by truncation of the full NBCn1 C-terminal tail (C-tail) yet did not require the C-terminal PDZ-binding motif (ETSL).