Positive feedback between Cdc42 activity and H+ efflux by the Na-H exchanger NHE1 for polarity of migrating cells

Christian Frantz, Anastasios Karydis, Perihan Nalbant, Klaus M. Hahn, Diane L. Barber

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)403-410
Number of pages8
JournalJournal of Cell Biology
Volume179
Issue number3
DOIs
StatePublished - Nov 5 2007
Externally publishedYes

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Cell Polarity
Sodium-Hydrogen Antiporter
Guanosine
Guanine Nucleotide Exchange Factors
Diphosphates
Cues
Fibroblasts
Eukaryotic Cells
Guanosine Triphosphate
Membranes

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Positive feedback between Cdc42 activity and H+ efflux by the Na-H exchanger NHE1 for polarity of migrating cells. / Frantz, Christian; Karydis, Anastasios; Nalbant, Perihan; Hahn, Klaus M.; Barber, Diane L.

In: Journal of Cell Biology, Vol. 179, No. 3, 05.11.2007, p. 403-410.

Research output: Contribution to journalArticle

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: Journal of Cell Biology. 2007 ; Vol. 179, No. 3. pp. 403-410.
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