Sodium-calcium exchanger 1 regulates epithelial cell migration via calcium-dependent extracellular signal-regulated kinase signaling.

The Journal of Biological Chemistry
Sona Lakshme BalasubramaniamSonali P Barwe

Abstract

Na(+)/Ca(2+) exchanger-1 (NCX1) is a major calcium extrusion mechanism in renal epithelial cells enabling the efflux of one Ca(2+) ion and the influx of three Na(+) ions. The gradient for this exchange activity is provided by Na,K-ATPase, a hetero-oligomer consisting of a catalytic α-subunit and a regulatory β-subunit (Na,K-β) that also functions as a motility and tumor suppressor. We showed earlier that mice with heart-specific ablation (KO) of Na,K-β had a specific reduction in NCX1 protein and were ouabain-insensitive. Here, we demonstrate that Na,K-β associates with NCX1 and regulates its localization to the cell surface. Madin-Darby canine kidney cells with Na,K-β knockdown have reduced NCX1 protein and function accompanied by 2.1-fold increase in free intracellular calcium and a corresponding increase in the rate of cell migration. Increased intracellular calcium up-regulated ERK1/2 via calmodulin-dependent activation of PI3K. Both myosin light chain kinase and Rho-associated kinase acted as mediators of ERK1/2-dependent migration. Restoring NCX1 expression in β-KD cells reduced migration rate and ERK1/2 activation, suggesting that NCX1 functions downstream of Na,K-β in regulating cell migration. In parallel, inhibition o...Continue Reading

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Citations

May 28, 2017·The Journal of Biological Chemistry·Sona Lakshme BalasubramaniamSonali P Barwe
Jul 15, 2015·American Journal of Physiology. Cell Physiology·Sona Lakshme BalasubramaniamSonali P Barwe
Sep 15, 2016·Cold Spring Harbor Molecular Case Studies·Niklas Smedemark-MarguliesJoseph Gonzalez-Heydrich
Jan 30, 2020·International Journal of Molecular Sciences·Antonio Villalobo, Martin W Berchtold
Feb 2, 2021·International Journal of Bipolar Disorders·Rif S El-MallakhPan You
Jun 17, 2021·Experimental and Therapeutic Medicine·Yong XieYang-Xin Chen

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