Journal
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 300, Issue 3, Pages C490-C495Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00280.2010
Keywords
cell migration; cell polarization; melanoma; NHE1; protons
Categories
Funding
- Deutsche Forschungsgemeinschaft [STO-54/3-2]
- Rolf-Dierichs-Stiftung
- University of Munster Medical School [MA 6 2 08 06]
- Danish Council for Independent Research
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Martin C, Pedersen SF, Schwab A, Stock C. Intracellular pH gradients in migrating cells. Am J Physiol Cell Physiol 300: C490-C495, 2011. First published December 9, 2010; doi:10.1152/ajpcell.00280.2010.-Cell polarization along the axis of movement is required for migration. The localization of proteins and regulators of the migratory machinery to either the cell front or its rear results in a spatial asymmetry enabling cells to simultaneously coordinate cell protrusion and retraction. Protons might function as such unevenly distributed regulators as they modulate the interaction of focal adhesion proteins and components of the cytoskeleton in vitro. However, an intracellular pH (pH(i)) gradient reflecting a spatial asymmetry of protons has not been shown so far. One major regulator of pH(i), the Na+/H+ exchanger NHE1, is essential for cell migration and accumulates at the cell front. Here, we test the hypothesis that the uneven distribution of NHE1 activity creates a pH(i) gradient in migrating cells. Using the pH-sensitive fluorescent dye BCECF, pH(i) was measured in five cell lines (MV3, B16V, NIH3T3, MDCK-F1, EA. hy926) along the axis of movement. Differences in pH(i) between the front and the rear end (Delta pH(i) front-rear) were present in all cell lines, and inhibition of NHE1 either with HOE642 or by absence of extracellular Na+ caused the pH(i) gradient to flatten or disappear. In conclusion, pH(i) gradients established by NHE1 activity exist along the axis of movement.
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