Molecular mechanism for targeting of NCX1 to basolateral membrane in renal epithelial cells

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Na+/Ca2+ exchanger type 1 (NCX1) bidirectionally exchanges 3 Na+ with 1 Ca2+, depending on the electrochemical gradients across the plasma membrane. In renal tubule, NCX1 is localized to the basolateral membranes of distal convoluted tubule cells, and is considered to be involved in Ca2+ reabsorption. However, the molecular mechanisms for its membrane sorting remain to be elucidated. In the present study, we found that the intracellular domain of NCX1 interacts with the adaptor protein. Using GST pull-down assays, we further identified the binding motif in NCX1 molecule. We also found that the mutations in the binding motif of NCX1 affect its membrane sorting in epithelial MDCK cells, suggesting the interaction between NCX1 and the adaptor protein plays a key role in NCX1 basolateral sorting.