Structure-function relationships of the NCKX2 Na+/Ca2+-K+ exchanger.

K+-dependent Na+/Ca2+ exchangers (NCKX) have been shown to play important roles in physiological processes as diverse as phototransduction in rod photoreceptors, motor learning and memory in mice, and skin pigmentation in humans. Most structure-function studies on NCKX proteins have been carried out on the NCKX2 isoform, but sequence similarity suggests that the results obtained with the NCKX2 isoform are likely to apply to all NCKX1-5 members of the human SLC24 gene family. Here we review our recent work on the NCKX2 protein concerning the topological arrangement of transmembrane segments carrying out cation transport, and concerning residues important for transport function and cation binding.