TY - JOUR
T1 - The Na+/H+ exchanger NHE1 is required for directional migration stimulated via PDGFR-alpha in the primary cilium
AU - Schneider, Linda
AU - Stock, Christian-Martin
AU - Dieterich, Peter
AU - Jensen, Bo Hammer
AU - Pedersen, Lotte Bang
AU - Satir, Peter
AU - Schwab, Albrecht
AU - Christensen, Søren Tvorup
AU - Pedersen, Stine Falsig
N1 - Keywords: Amiloride; Animals; Cation Transport Proteins; Cell Line; Cell Movement; Cilia; Interphase; Mice; NIH 3T3 Cells; Platelet-Derived Growth Factor; RNA, Messenger; Receptor, Platelet-Derived Growth Factor alpha; Signal Transduction; Sodium-Hydrogen Antiporter; Up-Regulation
PY - 2009
Y1 - 2009
N2 - 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 Tg737(orpk) 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 Tg737(orpk) 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.
AB - 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 Tg737(orpk) 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 Tg737(orpk) 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.
U2 - 10.1083/jcb.200806019
DO - 10.1083/jcb.200806019
M3 - Journal article
C2 - 19349585
SN - 0021-9525
VL - 185
SP - 163
EP - 176
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 1
ER -