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Related Experiment Videos

Transmethylation inhibitors decrease chemotactic sensitivity and delay cell aggregation in Dictyostelium discoideum.

A van Waarde, P J van Haastert

    Journal of Bacteriology
    |February 1, 1984
    PubMed
    Summary

    Protein methylation is crucial for Dictyostelium discoideum cell movement. Inhibiting transmethylation disrupts chemotaxis and aggregation by altering methylation responses to cyclic AMP (cAMP).

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    Area of Science:

    • Cellular Biology
    • Biochemistry
    • Developmental Biology

    Background:

    • Extracellular cyclic AMP (cAMP) is a key signaling molecule in Dictyostelium discoideum, mediating essential processes like chemotaxis and cell aggregation.
    • Cells exhibit a rapid, transient increase in protein carboxyl methylation in response to cAMP pulses, suggesting a role for methylation in signal transduction.

    Purpose of the Study:

    • To investigate the role of protein methylation in the chemotactic response of Dictyostelium discoideum to cyclic AMP (cAMP).
    • To determine how transmethylation inhibitors affect cAMP-induced chemotaxis and cell aggregation.

    Main Methods:

    • Utilized transmethylation inhibitors (cycloleucine, L-homocysteine thiolactone, coformycin) to assess their impact on Dictyostelium discoideum chemotaxis and aggregation.

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  • Measured changes in protein carboxyl methylation in response to cAMP stimulation under the influence of these inhibitors.
  • Evaluated the effect of inhibitors on cAMP binding and phosphodiesterase activity to rule out off-target effects.

    • Main Results:

    • Transmethylation inhibitors significantly decreased chemotactic sensitivity and delayed cell aggregation.
    • Inhibitors altered the transient positive methylation response to cAMP into a negative one by preferentially inhibiting methyltransferase over methylesterase.
    • The slow, late methylation response to cAMP remained unaffected by the inhibitors.

    Conclusions:

    • Protein methylation reactions are integral to the chemotactic signaling pathway in Dictyostelium discoideum.
    • The balance between protein methyltransferase and methylesterase activity, modulated by methylation, is critical for proper chemotaxis.
    • Targeting transmethylation offers a potential mechanism to disrupt Dictyostelium discoideum cell movement and aggregation.