Identification of the F1-ATPase at the cell surface of colonic epithelial cells: role in mediating cell proliferation

Aline Kowalski-Chauvel, Souad Najib, Irina G Tikhonova, Laurence Huc, Frederic Lopez, Laurent O Martinez, Elizabeth Cohen-Jonathan-Moyal, Audrey Ferrand, Catherine Seva

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

F1F0-ATPase was initially believed to be strictly expressed in the mitochondrial membrane. Interestingly, recent reports have shown that the F1 complex can serve as a cell surface receptor for apparently unrelated ligands. Here, we show for the first time the presence of the F1-ATPase at the cell surface of normal or cancerous colonic epithelial cells. Using Surface Plasmon Resonance technology and mass spectrometry, we identified a peptide hormone product of the gastrin gene (glycine-extended gastrin, G-gly), as a new ligand for the F1-ATPase. By molecular modeling, we identified the motif in the peptide sequence (EE/DxY), which directly interacts with the F1-ATPase and the amino-acids in the F1-ATPase which bind this motif. Replacement of the E9 residue by an alanine in the EE/DxY motif resulted in a strong decrease of G-gly binding to the F1-ATPase and the loss of its biological activity. In addition we demonstrated that F1-ATPase mediates the growth effects of the peptide. Indeed, blocking ATPase activity decreases G-gly-induced cell growth. The mechanism likely involves ADP production by the membrane F1-ATPase which is induced by G-gly. These results suggest an important contribution of cell surface ATPase in the pro-proliferative action of this gastrointestinal peptide.
Original languageEnglish
Pages (from-to)41458-41468
Number of pages11
JournalJournal of Biological Chemistry
Volume287
Issue number49
DOIs
Publication statusPublished - 30 Nov 2012

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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