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This Article Free via Open Access: OA OA Full Text Full Text (PDF) Supplementary Data OA All Versions of this Article: 585/2/351    most recent jphysiol.2007.145185v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stüwe, L. Articles by Stock, C. Search for Related Content PubMed PubMed Citation Articles by Stüwe, L. Articles by Stock, C. Related Collections Cellular

¹ Institute of Physiology II, University of Münster, Robert-Koch-Str. 27b, D-48149 Münster, Germany
² Departement de Physiologie, Université de Montréal, CP 6128, Succursale Centre-Ville Montréal, Québec H3C 3J7, Canada

Migration and morphology of human melanoma cells (MV3) depend on extracellular pH (pH_e) and the activity of the Na⁺/H⁺ exchanger NHE1. To distinguish effects of NHE1 activity per se from effects of pH_e we compared an NHE1-deficient mutant with rescued and wild-type cells. Time lapse video microscopy was used to investigate migratory and morphological effects caused by pH_e and NHE1 activity, and a membrane-bound fluorescein conjugate was employed for ratiometric pH measurements at the outer leaflet of the cell membrane. As long as NHE1 remained inactive due to deficiency or inhibition by cariporide (HOE642) neither migration nor morphology was affected by changes in pH_e. Under these conditions pH at the outer leaflet of the plasma membrane was uniform all over the cell surface. The typical pH dependence of MV3 cell migration and morphology could be reconstituted by restoring NHE1 activity. At the same time the proton gradient at the outer leaflet of the plasma membrane with the higher proton concentration at the leading edge and the lower one at the cell rear was re-established as well. Hence, NHE1 activity generates a proton gradient at the cell surface accompanied by the cells' ability to respond to changes in pH_e (bulk pH). We conclude that NHE1 activity contributes to the generation of a well-defined cell surface pH by creating a proton gradient at the outer leaflet of the plasma membrane that is needed for (i) the development of a variety of morphologies including a distinct polarity and (ii) migration. A missing proton gradient at the cell surface cannot be compensated for by varying pH_e.

(Received 18 September 2007; accepted after revision 3 October 2007; first published online 4 October 2007)
Corresponding author C. Stock: Institute of Physiology II, University of Münster, Robert-Koch-Str. 27b, D-48149 Münster, Germany. Email: cmstock{at}uni-muenster.de

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