Members of the SLC24 gene family encode K(+)-dependent Na(+)/Ca(2+) exchangers (NCKX) that utilize both the inward Na(+) and outward K(+) gradients to extrude Ca(2+) from cells. There are five human SLC24 genes that play a role in biological process as diverse as vision in retinal rod and cone photoreceptors, olfaction, skin pigmentation and at least three of the five genes are also widely expressed in the brain. Here I review the functional, physiological and structural features of NCKX proteins that have emerged in the past few years.
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Na+/Ca2+ exchange in enamel cells is dominated by the K+-dependent NCKX exchanger.
J Gen Physiol
January 2024
Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY, USA.
Calcium (Ca2+) extrusion is an essential function of the enamel-forming ameloblasts, providing Ca2+ for extracellular mineralization. The plasma membrane Ca2+ ATPases (PMCAs) remove cytosolic Ca2+ (cCa2+) and were recently shown to be efficient when ameloblasts experienced low cCa2+ elevation. Sodium-calcium (Na+/Ca2+) exchange has higher capacity to extrude cCa2+, but there is limited evidence on the function of the two main families of Na+/Ca2+ exchangers in enamel formation.
View Article and Find Full Text PDFCalmodulin binds and modulates K-dependent Na/Ca-exchanger isoform 4, NCKX4.
J Biol Chem
August 2021
Department of Biochemistry & Molecular Biology, Libin Cardiovascular Institute and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. Electronic address:
The family of K-dependent Na/Ca-exchangers, NCKX, are important mediators of cellular Ca efflux, particularly in neurons associated with sensory transduction. The NCKX family comprises five proteins, NCKX1-5, each being the product of a different SLC24 gene. NCKX4 (SLC24A4) has been found to have a critical role in termination and adaptation of visual and olfactory signals, melanocortin-dependent satiety signaling, and the maturation of dental enamel.
View Article and Find Full Text PDFStructure-function relationships of K-dependent Na/Ca exchangers (NCKX).
Cell Calcium
March 2020
Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada. Electronic address:
K-dependent Na/Ca exchanger proteins (NCKX1-5) of the SLC24 gene family play important roles in a wide range of biological processes including but not limited to rod and cone photoreceptor vision, olfaction, enamel formation and skin pigmentation. NCKX proteins are also widely expressed throughout the brain and NCKX2 and NCKX4 knockouts in mice have specific phenotypes. Here we review our work on structure-function relationships of NCKX proteins.
View Article and Find Full Text PDFExpression of potassium-dependent sodium-calcium exchanger in the murine lens.
Exp Eye Res
February 2018
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8096, St. Louis, MO 63110, USA. Electronic address:
Loss of intracellular calcium homeostasis may contribute to the opacification of lens tissue during cortical cataract formation. In healthy lenses, the concentration of intracellular calcium is maintained at levels far below electrochemical equilibrium but the identity of the calcium extrusion mechanism in lens fiber cells has remained elusive. Previous studies focused on the role of plasma membrane calcium ATPases and sodium-calcium exchangers.
View Article and Find Full Text PDFIdentification and Characterization of K(+)-Dependent Na(+)-Ca(2+) Exchange Transport in Pigmented MEB4 Cells Mediated by NCKX4.
Biochemistry
May 2016
Department of Physiology & Pharmacology, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary T2N 4N1, Canada.
The SLC24 gene family encodes K(+)-dependent Na(+)-Ca(2+) exchangers or NCKX proteins. The NCKX4 and NCKX5 isoforms have been shown to be important for pigmentation, and single nucleotide polymorphism (SNP) in both alleles of the SLC24a5 gene is the major genetic determinant for light skin in Caucasians. NCKX4 is thought to operate in the surface membrane of cells, whereas NCKX5 is thought to be located in intracellular membranes.
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