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Pertussis and cholera toxin ADP-ribosylation in Dictyostelium discoideum membranes

L Khachatrian1, C Klein, A Howlett

  • 1Department of Pharmacology, St. Louis University School of Medicine, St. Louis, MO 63104.

Insights

Researchers identified a novel 39 kDa G-protein in Dictyostelium discoideum membranes. This protein is a substrate for cholera and pertussis toxins, suggesting a role in cellular signaling pathways.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Dictyostelium discoideum (D. discoideum) is a model organism for studying cellular processes.
  • G proteins are key regulators of cellular signaling pathways.
  • Cholera toxin and pertussis toxin are bacterial toxins that ADP-ribosylate specific G proteins, altering their function.

Purpose of the Study:

  • To identify and characterize novel G proteins in D. discoideum membranes.
  • To investigate the substrate specificity and regulation of ADP-ribosylation by cholera and pertussis toxins in D. discoideum.
  • To explore the potential role of a novel G protein in D. discoideum signaling.

Main Methods:

  • Membrane preparation from D. discoideum.
  • ADP-ribosylation assays using cholera toxin and pertussis toxin.
  • Co-migration analysis with known G protein subunits (Gs and Gi) from mammalian cells.
  • Investigation of the effects of GTP analogs and divalent cations on ADP-ribosylation.

Main Results:

  • A 39 kDa protein substrate for both cholera and pertussis toxins was identified in D. discoideum membranes.
  • This 39 kDa protein did not co-migrate with alpha subunits of mammalian Gs or Gi proteins.
  • GTP analogs enhanced cholera toxin-mediated ADP-ribosylation but had minimal effect on pertussis toxin-mediated ADP-ribosylation.
  • Divalent cations inhibited ADP-ribosylation by both toxins.

Conclusions:

  • A novel G protein, distinct from mammalian Gs and Gi, exists in D. discoideum membranes.
  • This novel G protein is a substrate for cholera and pertussis toxins, indicating its involvement in cellular signaling.
  • The unique regulatory properties suggest potential association with D. discoideum adenylate cyclase or regulation of cAMP receptor-mediated responses.

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