SLC24A1 Membrane Protein Introduction

Introduction of SLC24A1

Sodium/potassium/calcium exchanger 1 (SLC24A1) is a protein that in humans is encoded by the SLC24A1 gene. SLC24A1 is a considerably larger protein with 1098 residues. SLC24A1 appears to have the most restricted tissue distribution and is only found in retinal ROS and in platelets. All four full-length members of the human NCKX gene family, as well as related proteins found in lower organisms, are predicted to contain two large hydrophilic loops and two sets of multiple transmembrane spanning segments.

Basic Information of SLC24A1
Protein Name Sodium/potassium/calcium exchanger 1
Gene Name SLC24A1
Aliases Na(+)/K(+)/Ca(2+)-exchange protein 1, Retinal rod Na-Ca+K exchanger, Solute carrier family 24 member 1, KIAA0702, NCKX1
Organism Homo sapiens (Human)
UniProt ID O60721
Transmembrane Times 11
Length (aa) 1099

Function of SLC24A1 Membrane Protein

Na+/Ca2+-K+ exchange (NCKX) was first discovered in the outer segments of vertebrate rod photoreceptors, where it is the only mechanism for extruding the Ca2+ that enters ROS via the light-sensitive and cGMP-gated channels. SLC24A1 and SLC24A2 are bidirectional transporters normally extruding Ca2+ from the cell (forward exchange), but also able to carry Ca2+ into the cell (reverse exchange) when the transmembrane Na+ gradient is reversed. Expression of SLC24A1 was restricted to photoreceptors and that the particular properties of this protein have evolved to suit the special requirements for calcium homeostasis in this environment. In the absence of any Ca2+ influx, Na+/Ca2+-K+ exchange is expected to lower cytosolic Ca2+ to less than 2 nM, yet this is not observed in ROS. After a short burst of operation at full rate, SLC24A1 appears to become nearly completely inactivated, and this mechanism appears to prevent intracellular free Ca2+ from dropping below 2 nM when rod photoreceptors are saturated for prolonged periods of time during bright daylight illumination.

Model of potential roles for calcium in erythroid enucleation. Fig.1 Model of potential roles for calcium in erythroid enucleation. (Wölwer, 2016)

Application of SLC24A1 Membrane Protein in Literature

  1. Jalloul A.H., et al. Cation dependencies and turnover rates of the human K⁺-dependent Na⁺-Ca2+ exchangers NCKX1, NCKX2, NCKX3 and NCKX4. Cell Calcium. 2016, 59(1): 1-11. PubMed ID: 26631410

    The article reveals that the turnover rate of NCKX2 exchanger is three (NCKX4) to five times higher (NCKX1 and NCKX3) compared with the other NCKX isoforms. The turnover number of the purified bovine NCKX1 is previously determined to be - 30 Ca2+ /s/exchanger.

  2. Vinberg F., et al. A new mouse model for stationary night blindness with mutant Slc24a1 explains the pathophysiology of the associated human disease. Hum Mol Genet. 2015, 24(20): 5915-5929. PubMed ID: 25821969

    The authors show that lack of NCKX1 does not compromise the background light adaptation of rod photoreceptors, suggesting additional Ca(2+)-extruding mechanisms exist in these cells.

  3. Schnetkamp P.P., et al. The SLC24 family of K⁺-dependent Na⁺-Ca²⁺ exchangers: structure-function relationships. Curr Top Membr. 2014, 73: 263-287. PubMed ID: 24745986

    The authors conclude that for three of the dolphin NCKX1 proteins, the signal peptide is cleaved for about 50% of the total amount of NCKX protein expressed.

  4. Kang K., et al. Signal sequence cleavage and plasma membrane targeting of the retinal rod NCKX1 and cone NCKX2 Na+/Ca2+- K+ exchangers. Oncol Lett. 2003, 42(31): 9438-9445. PubMed ID: 12899631

    This article demonstrates that deletion of the signal sequence in both dolphin rod NCKX1 or cone NCKX2 does not affect NCKX protein synthesis but disrupts plasma membrane targeting as judged from the abolition of NCKX function and from lack of surface biotinylation.

  5. Poon S., et al. Alternatively spliced isoforms of the rat eye sodium/calcium+ potassium exchanger NCKX1. Am J Physiol Cell Physiol. 2000, 278(4): C651-660. PubMed ID: 10751314

    The authors discover that recombinant rat NCKX1 protein is tagged in the extracellular loop with the FLAG epitope and expressed in HEK-293 cells.

SLC24A1 Preparation Options

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  1. Wölwer C B, et al. (2016). Calcium Signaling Is Required for Erythroid Enucleation. PLoS One. e014201.

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