The Na/Ca‐K Exchanger Gene Family

Abstract

Ca2+ extrusion driven by both the inward Na+ gradient as well as the outward K+ gradient is essential for visual transduction in retinal rod and cone photoreceptors because it removes Ca2+ that enters photoreceptors via the cGMP‐gated and light‐sensitive channels. We have cloned rod and cone Na/Ca‐K exchanger (NCKX) cDNAs from several species, and we have cloned NCKX cDNAs from lower organisms that lack vertebrate‐type vision. Although in situ NCKX physiology has only been documented for vertebrate photoreceptors, it is now clear that NCKX gene products have a much broader distribution pattern. Here, we review some of the structural and functional features that have emerged from our studies on different members of the NCKX gene family.

Sodium–calcium exchangers contribute to the regulation of cytosolic calcium levels in mouse taste cells

“…We also tested for the expression of sodium–calcium–potassium exchangers (NCKXs) which exchange sodium ions for calcium ions in a potassium‐dependent manner (Cervetto et al 1989; Dong et al 2001; Prinsen et al 2002; Szerencsei et al 2002). There are six identified NCKX isoforms (NCKX1–6) (Prinsen et al 2002; Szerencsei et al 2002; Cai & Lytton, 2004) of which we were able to amplify PCR products for NCKX1–3 and NCKX6 (Fig. 6) in taste cells.…”

“…This study is the first to describe the presence of sodium–calcium exchangers in taste cells and reports on their unique function in the regulation of cytosolic calcium in these cells. While many cells rely on NCXs to recover from stimulus‐evoked calcium increases (Blaustein & Lederer, 1999; Prinsen et al 2002; Szerencsei et al 2002; Schnetkamp, 2004; Iwamoto et al 2007), in taste cells NCX activity is important for the regulation of cytosolic calcium even in the absence of cell stimulation. This is due to the presence of a constitutive calcium influx in taste cells that is also regulated in part by mitochondrial calcium transport (Hacker & Medler, 2008).…”

A novel nonsense variant in SLC24A4 causing a rare form of amelogenesis imperfecta in a Pakistani family

“…Five functionally different types of K + -dependent Na + / Ca + 2 exchangers (NCKX1-5) have been characterized in humans [32,33]. NCKXs are bidirectional membrane transporters; for example, NCKX4 transports an intracellular Ca + 2 and a K + ion in exchange for four extracellular Na + ions [34].…”

“…SLC24A4 (OMIM 609840) encodes a protein of 622 amino acids, called solute carrier family 24 member 4 (SLC24A4), which is one of the members of K +dependent Na + /Ca 2+ exchanger family (SLC24A), comprising a total of five members. It has been mapped to the chromosome 14q32 [33,36]. SLC24A4 has various transcripts (NM_153646, NM_153647, NM_153648) resulting from alternative splicing and the longest isoform (NM_153646) contains 17 coding exons.…”

Structure–Function Relationships of the NCKX2 Na+/Ca2+‐K+ Exchanger

“…In order to select (blocks of) residues for mutagenesis experiments we first carried out “selection through evolution,” that is, we compared cation dependencies and K + transport of NCKX proteins from various species ranging from mammals to worms as well as from a mutant NCKX1 protein from which the two large hydrophilic loops were deleted 24,26,33 . Cation dependencies were found to be very similar suggesting that domains/residues conserved between all these NCKX proteins are responsible for cation binding and cation transport.…”