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

• Published in: The Journal of cell biology Vol. 185; no. 1; p. 163
• Main Authors: Schneider, Linda, Stock, Christian-Martin, Dieterich, Peter, Jensen, Bo Hammer, Pedersen, Lotte Bang, Satir, Peter, Schwab, Albrecht, Christensen, Søren Tvorup, Pedersen, Stine Falsig
• Format: Journal Article
• Language: English
• Published: New York Rockefeller University Press 06.04.2009
• Subjects: Cell adhesion & migration; Cells; Hydrogen; Ribonucleic acid; RNA; Rodents; Sodium
• ISSN: 0021-9525; 1540-8140

We previously demonstrated that the primary cilium coordinates platelet-derived growth factor (PDGF) receptor (PDGFR) α-mediated migration in growth-arrested fibroblasts. In this study, we investigate the functional relationship between ciliary PDGFR-α and the .../... 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 Tg737... MEFs, which have no or very short primary cilia. In growth-arrested NIH3T3 cells, NHE1 is activated by the specific PDGFR-α 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 Tg737... MEFs. PDGF-AA failed to stimulate migration in NHE1-null fibroblasts. In conclusion, stimulation of directional migration in response to ciliary PDGFR-α signals is specifically dependent on NHE1 activity, indicating that NHE1 activation is a critical event in the physiological response to PDGFR-α stimulation. (ProQuest: ... denotes formulae/symbols omitted.)