A functional approach to understanding the role of NCKX5 in Xenopus pigmentation

Williams, Ruth, Winkfein, Robert, Ginger, Rebecca, Green, Martin, Schnetkamp, Paul and Wheeler, Grant ORCID: https://orcid.org/0000-0002-4335-8577 (2017) A functional approach to understanding the role of NCKX5 in Xenopus pigmentation. PLoS One, 12 (7). ISSN 1932-6203

[thumbnail of Published manuscript]
Preview
PDF (Published manuscript) - Published Version
Available under License Creative Commons Attribution.

Download (12MB) | Preview

Abstract

NCKX5 is an ion exchanger expressed mostly in pigment cells; however, the functional role for this protein in melanogenesis is not clear. A variant allele of SLC24A5, the gene encoding NCKX5, has been shown to correlate with lighter skin pigmentation in humans, indicating a key role for SLC24A5 in determining human skin colour. SLC24A5 expression has been found to be elevated in melanoma. Knockdown analyses have shown SLC24A5 to be important for pigmentation, but to date the function of this ion exchanger in melanogenesis has not been fully established. Our data suggest NCKX5 may have an alternative activity that is key to its role in the regulation of pigmentation. Here Xenopus laevis is employed as an in vivo model system to further investigate the function of NCKX5 in pigmentation. SLC24A5 is expressed in the melanophores as they differentiate from the neural crest and develop in the RPE of the eye. Morpholino knockdown and rescue experiments were designed to elucidate key residues and regions of the NCKX5 protein. Unilateral morpholino injection at the 2 cell stage resulted in a reduction of pigmentation in the eye and epidermis of one lateral side of the tadpole. Xenopus and human SLC24A5 can rescue the morpholino effects. Further rescue experiments including the use of ion exchange inactive SLC24A5 constructs raise the possibility that full ion exchanger function of NCKX5 may not be required for rescue of pigmentation.

Item Type: Article
Uncontrolled Keywords: nckx5,pigmentation,xenopus,slc24a5
Faculty \ School: Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Science > Research Groups > Cells and Tissues
Faculty of Science > Research Groups > Wheeler Group
Related URLs:
Depositing User: Pure Connector
Date Deposited: 13 Jul 2017 05:06
Last Modified: 20 Apr 2023 00:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/64105
DOI: 10.1371/journal.pone.0180465

Downloads

Downloads per month over past year

Actions (login required)

View Item View Item