Structure-function relationships of K-dependent Na/Ca exchangers (NCKX).

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.

Residues important for Ca ion transport in the neuronal K-dependent Na-Ca exchanger (NCKX2).

K-dependent Na-Ca exchangers (NCKXs) belong to Ca/cation antiporter gene superfamily. NCKX proteins play an important role in Ca homeostasis and are bi-directional plasma membrane Ca-transporters which utilize the inward Na and outward K gradients to move Ca ions into and out of the cytosol (4Na:1Ca + 1 K). In this study, we examined residues in the two regions with the highest degree of homology between the different NCKX isoforms (α-1 and α-2 repeats) to determine which residues are important for Ca coordination.

Cellular localization of the K -dependent Na -Ca exchanger NCKX5 and the role of the cytoplasmic loop in its distribution in pigmented cells.

NCKX5 is a bidirectional K -dependent Na -Ca exchanger, which belongs to the SLC24A gene family. In particular, the A111T mutation of NCKX5 has been associated with reduced pigmentation in European populations. In contrast to other NCKX isoforms, which function in the plasma membrane (PM), NCKX5 has been shown to localize either in the trans-Golgi network (TGN) or in melanosomes.

Residues important for K ion transport in the K-dependent Na-Ca exchanger (NCKX2).

K-dependent Na-Ca exchangers (NCKXs) play an important role in Ca homeostasis in many tissues. NCKX proteins are bi-directional plasma membrane Ca-transporters which utilize the inward Na and outward K gradients to move Ca ions into and out of the cytosol (4Na:1Ca + 1 K). In this study, we carried out scanning mutagenesis of all the residues of the highly conserved α-1 and α-2 repeats of NCKX2 to identify residues important for K transport.

ATP triggers a robust intracellular [Ca ]-mediated signalling pathway in human synovial fibroblasts.

New Findings: What is the central question of this study? What are the main [Ca ] signalling pathways activated by ATP in human synovial fibroblasts? What is the main finding and its importance? In human synovial fibroblasts ATP acts through a linked G-protein (G ) and phospholipase C signalling mechanism to produce IP , which then markedly enhances release of Ca from the endoplasmic reticulum. These results provide new information for the detection of early pathophysiology of arthritis.

Abstract: In human articular joints, synovial fibroblasts (HSFs) have essential physiological functions that include synthesis and secretion of components of the extracellular matrix and essential articular joint lubricants, as well as release of paracrine substances such as ATP.