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- Title
Positive feedback between Cdc42 activity and H<sup>+</sup> efflux by the Na-H exchanger NHE1 for polarity of migrating cells.
- Authors
Frantz, Christian; Karydis, Anastasios; Nalbant, Perihan; Hahn, Klaus M.; Barber, Diane L.
- Abstract
A fundamental feature of cell polarity in response to spatial cues is asymmetric amplification of molecules generated by positive feedback signaling. We report a positive feedback loop between the guanosine triphosphatase Cdc42, a central determinant in eukaryotic cell polarity, and H+ efflux by Na-H+ exchanger 1 (NHE1), which is necessary at the front of migrating cells for polarity and directional motility. In response to migratory cues, Cdc42 is not activated in fibroblasts expressing a mutant NHE1 that lacks H+ efflux, and wild-type NHE1 is not activated in fibroblasts expressing mutationally inactive Cdc42-N17. H+ efflux by NHE1 is not necessary for release of Cdc42-guanosine diphosphate (GDP) from Rho GDP dissociation inhibitor or for the membrane recruitment of Cdc42 but is required for GTP binding by Cdc42 catalyzed by a guanine nucleotide exchange factor (GEF). Data indicate that GEF binding to phosphotidylinositol 4,5-bisphosphate is pH dependent, suggesting a mechanism for how H+ efflux by NHE1 promotes Cdc42 activity to generate a positive feedback signal necessary for polarity in migrating cells.
- Publication
Journal of Cell Biology, 2007, Vol 179, Issue 3, p403
- ISSN
0021-9525
- Publication type
Academic Journal
- DOI
10.1083/jcb.200704169