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Published online
doi:10.1083/jcb.200806019
The Journal of Cell Biology, Vol. 185, No. 1, 163-176
The Rockefeller University Press, 0021-9525 $30.00
© Schneider et al.
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Article

The Na+/H+ exchanger NHE1 is required for directional migration stimulated via PDGFR-{alpha} in the primary cilium



Linda Schneider1, Christian-Martin Stock2, Peter Dieterich3, Bo Hammer Jensen1, Lotte Bang Pedersen1, Peter Satir4, Albrecht Schwab2, Søren Tvorup Christensen1, and Stine Falsig Pedersen1

1 Department of Biology, University of Copenhagen, DK-2100 Copenhagen O, Denmark
2 Institut für Physiologie, Universität Münster, D-48149 Münster, Germany
3 Institut für Physiologie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
4 Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461

Correspondence to Stine Falsig Pedersen: sfpedersen{at}bio.ku.dk

We previously demonstrated that the primary cilium coordinates platelet-derived growth factor (PDGF) receptor (PDGFR) {alpha}–mediated migration in growth-arrested fibroblasts. In this study, we investigate the functional relationship between ciliary PDGFR-{alpha} and the Na+/H+ exchanger NHE1 in directional cell migration. NHE1 messenger RNA and protein levels are up-regulated in NIH3T3 cells and mouse embryonic fibroblasts (MEFs) during growth arrest, which is concomitant with cilium formation. NHE1 up-regulation is unaffected in Tg737orpk MEFs, which have no or very short primary cilia. In growth-arrested NIH3T3 cells, NHE1 is activated by the specific PDGFR-{alpha} ligand PDGF-AA. In wound-healing assays on growth-arrested NIH3T3 cells and wild-type MEFs, NHE1 inhibition by 5'-(N-ethyl-N-isopropyl) amiloride potently reduces PDGF-AA–mediated directional migration. These effects are strongly attenuated in interphase NIH3T3 cells, which are devoid of primary cilia, and in Tg737orpk MEFs. PDGF-AA failed to stimulate migration in NHE1-null fibroblasts. In conclusion, stimulation of directional migration in response to ciliary PDGFR-{alpha} signals is specifically dependent on NHE1 activity, indicating that NHE1 activation is a critical event in the physiological response to PDGFR-{alpha} stimulation.


© 2009 Schneider et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

This work was presented at the American Society for Cell Biology meeting in Washington, DC, on 5 December 2007 and has appeared in abstract form.

Abbreviations used in this paper: ANOVA, analysis of variance; EIPA, 5'-(N-ethyl-N-isopropyl) amiloride; gas, growth arrest specific; MEF, mouse embryonic fibroblast; PDGFR, PDGF receptor; pHi, intracellular pH; WT, wild type.



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