A gated relaxation oscillator mediated by FrzX controls morphogenetic movements in Myxococcus xanthus


Dynamic control of cell polarity is of critical importance for many aspects of cellular development and motility. In Myxococcus xanthus, MglA, a G protein, and MglB, its cognate GTPase-activating protein, establish a polarity axis that defines the direction of movement of the cell and that can be rapidly inverted by the Frz chemosensory system. Although vital for collective cell behaviours, how Frz triggers this switch has remained unknown. Here, we use genetics, imaging and mathematical modelling to show that Frz controls polarity reversals via a gated relaxation oscillator. FrzX, which we identify as a target of the Frz kinase, provides the gating and thus acts as the trigger for reversals. Slow relocalization of the polarity protein RomR then creates a refractory period during which another switch cannot be triggered. A secondary Frz output, FrzZ, decreases this delay, allowing rapid reversals when required. Thus, this architecture results in a highly tuneable switch that allows a wide range of reversal frequencies.

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Fig. 1: Pole-to-pole dynamics of the polarity proteins.
Fig. 2: A three-protein relaxation oscillator model of polarity reversals.
Fig. 3: FrzX, not RomR, is the major FrzE kinase substrate used to control the reversal cycle.
Fig. 4: FrzX-P acts at the lagging cell pole.
Fig. 5: Reversals require the action of both FrzX-P and RomR at the lagging cell pole.
Fig. 6: A gated relaxation oscillator model of the polarity-switching mechanism captures most of the experimental data.


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We thank L. Sogaard-Andersen and U. Gerland for discussions and V. Sourjik for comments on the manuscript. M.G. was the recipient of an ARC fellowship (DOC20140601482). E.M. is the recipient of an AMIDEX “Académie d’excellence” thesis fellowship (no. ANR-11-IDEX-0001-02). S.L. is funded by an ANR programme “BACTOCOMPASS”. T.M. is the recipient of an ERC starting grant “DOME 261105” and an ANR programme “BACTOCOMPASS”. R.V. was supported by the French Infrastructure for Integrated Structural Biology (FRISBI) ANR-10-INBS-05.

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M.G., S.M.M., E.M., S.L., M.H. and T.M. conceptualized the study. M.G., S.M.M., E.M., S.L., V.M., M.H. and T.M. conceptualized the methodology. M.G., S.M.M., E.M., S.L., L.M., G.B. and Y.Z. conducted the investigation. M.H. and T.M. wrote the original draft of the manuscript. M.G., S.M.M. and E.M. reviewed and edited the manuscript. M.G., S.M.M., E.M., S.L., L.E., M.H. and T.M. conducted the visualization experiments. M.H. and T.M. acquired funding. B.P.B., R.V., J.W.S. and M.V. provided resources. S.M.M. and M.H. conducted the mathematical analysis. M.H. and T.M. provided supervision.

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Correspondence to Martin Howard or Tâm Mignot.

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Guzzo, M., Murray, S.M., Martineau, E. et al. A gated relaxation oscillator mediated by FrzX controls morphogenetic movements in Myxococcus xanthus. Nat Microbiol 3, 948–959 (2018). https://doi.org/10.1038/s41564-018-0203-x

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