期刊
JOURNAL OF CELL BIOLOGY
卷 185, 期 1, 页码 163-176出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200806019
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- NIDDK NIH HHS [P01 DK041918, DK41296, DK41918, P30 DK041296, P30 DK074038] Funding Source: Medline
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.
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