Modulation of cell motility by spatial repositioning of enzymatic ATP/ADP exchange capacity.
until further notice
SourceJournal of Biological Chemistry, 284, 3, (2009), pp. 1620-1627
Article / Letter to editor
Display more detailsDisplay less details
Cell Biology (UMC)
Journal of Biological Chemistry
SubjectIGMD 8: Mitochondrial medicine; NCMLS 2: Immune Regulation; NCMLS 4: Energy and redox metabolism; NCMLS 5: Membrane transport and intracellular motility; ONCOL 3: Translational research
ATP is the "principal energy currency" in metabolism and the most versatile small molecular regulator of cellular activities. Although already much is known about the role of ATP in fundamental processes of living systems, data about its compartmentalization are rather scarce, and we still have only very limited understanding of whether patterns in the distribution of intracellular ATP concentration ("ATP inhomogeneity") do exist and have a regulatory role. Here we report on the analysis of coupling of local ATP supply to regulation of actomyosin behavior, a widespread and dynamic process with conspicuous high ATP dependence, which is central to cell shape changes and cell motility. As an experimental model, we use embryonic fibroblasts from knock-out mice without major ATP-ADP exchange enzymes, in which we (re)introduce the ATP/ADP exchange enzyme adenylate kinase-1 (AK1) and deliberately manipulate its spatial positioning by coupling to different artificial location tags. By transfection-complementation of AK1 variants and comparison with yellow fluorescent protein controls, we found that motility and spreading were enhanced in cells with AK1 with a focal contact guidance tag. Intermediary enhancement was observed in cells with membrane-targeted or cytosolic AK1. Use of a heterodimer-inducing approach for transient translocation of AK1 to focal contacts under conditions of constant global AK1 activity in the cell corroborated these results. Based on our findings with these model systems, we propose that local ATP supply in the cell periphery and "on site" fuelling of the actomyosin machinery, when maintained via enzymes involved in phosphoryl transfer, are codetermining factors in the control of cell motility.
Upload full text
Use your RU credentials (u/z-number and password) tolog in with SURFconextto upload a file for processing by the repository team.