Frantz, Christian; Karydis, Anastasios; Nalbant, Perihan; Hahn, Klaus M.; Barber, Diane L.:
Positive feedback between Cdc42 activity and H+ efflux by the Na-H exchanger NHE1 for polarity of migrating cells
In: The Journal of Cell Biology (JCB), Jg. 179 (2007), Heft 3, S. 403 - 410
2007Artikel/Aufsatz in Zeitschrift
BiologieFakultät für Biologie
Damit verbunden: 1 Publikation(en)
Titel:
Positive feedback between Cdc42 activity and H+ efflux by the Na-H exchanger NHE1 for polarity of migrating cells
Autor*in:
Frantz, Christian;Karydis, Anastasios;Nalbant, PerihanUDE
LSF ID
49819
ORCID
0000-0002-5649-5933ORCID iD
Sonstiges
der Hochschule zugeordnete*r Autor*in
;
Hahn, Klaus M.;Barber, Diane L.
Erscheinungsjahr:
2007

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.