The GPI-anchored superoxide dismutase SodC is essential for regulating basal Ras activity and for chemotaxis of Dictyostelium discoideum.

A genetic screen for Dictyostelium mutant displaying high level of constitutive phosphatidylinositol (3,4,5)-trisphosphate led to the finding that the glycosylphosphatidylinositol (GPI)-anchored superoxide dismutase SodC regulates small GTPase Ras. Cells that lack SodC exhibited constitutively high levels of active Ras, more membrane localization of GFP-PHcrac, and defects in chemoattractant sensing, cell polarization and motility. These defects of SodC-lacking cells were partially restored by expression of wild-type SodC but not by the catalytically inactive mutant SodC (H245R, H247Q). Furthermore, an inhibition of PI3K activity in SodC-deficient cells by LY294002 only partially restored chemoattractant sensing and cell polarization, consistent with the fact that SodC-deficient cells have aberrantly high level of active Ras, which functions upstream of PI3K. A higher level of active GFP-RasG was observed in SodC-deficient cells, which significantly decreased upon incubation of SodC-deficient cells with the superoxide scavenger XTT. Having constitutively high levels of active Ras proteins and more membrane localization of GFP-PHcrac, SodC-deficient cells exhibited severe defects in chemoattractant sensing, cell polarization and motility.

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