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Protein-protein interaction network controlling establishment and maintenance of switchable cell polarity

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  • Luís António Menezes Carreira
  • Filipe Tostevin
  • Ulrich Gerland
  • Lotte Søgaard-Andersen

Abstract

Cell polarity underlies key processes in all cells, including growth, differentiation and division. In the bacterium Myxococcus xanthus, front-rear polarity is crucial for motility. Notably, this polarity can be inverted, independent of the cell-cycle, by chemotactic signaling. However, a precise understanding of the protein network that establishes polarity and allows for its inversion has remained elusive. Here, we use a combination of quantitative experiments and data-driven theory to unravel the complex interplay between the three key components of the M. xanthus polarity module. By studying each of these components in isolation and their effects as we systematically reconstruct the system, we deduce the network of effective interactions between the polarity proteins. RomR lies at the root of this network, promoting polar localization of the other components, while polarity arises from interconnected negative and positive feedbacks mediated by the small GTPase MglA and its cognate GAP MglB, respectively. We rationalize this network topology as operating as a spatial toggle switch, providing stable polarity for persistent cell movement whilst remaining responsive to chemotactic signaling and thus capable of polarity inversions. Our results have implications not only for the understanding of polarity and motility in M. xanthus but also, more broadly, for dynamic cell polarity.Author summary: The asymmetric localization of cellular components (polarity) is at the core of many important cellular functions including growth, division, differentiation and motility. However, important questions still remain regarding the design principles underlying polarity networks and how their activity can be controlled in space and time. We use the rod-shaped bacterium Myxococcus xanthus as a model to study polarity and its regulation. Like many bacteria, in M. xanthus a well-defined front-rear polarity axis enables efficient translocation. This polarity axis is defined by asymmetric polar localization of a switch-like GTPase and its cognate regulators, and can be reversed in response to signaling cues. Here we use a combination of quantitative experiments and data-driven theory to deduce the network of interactions among the M. xanthus polarity proteins and to show how the combination of positive- and negative-feedback interactions give rise to asymmetric polar protein localization. We rationalize this network topology as operating as a spatial toggle switch, providing stable polarity for persistent cell movement whilst remaining responsive to chemotactic signaling and capable of polarity inversions. Our results have broader implications for our understanding of dynamic cell polarity and GTPase regulation in both bacteria and eukaryotic cells.

Suggested Citation

  • Luís António Menezes Carreira & Filipe Tostevin & Ulrich Gerland & Lotte Søgaard-Andersen, 2020. "Protein-protein interaction network controlling establishment and maintenance of switchable cell polarity," PLOS Genetics, Public Library of Science, vol. 16(6), pages 1-30, June.
  • Handle: RePEc:plo:pgen00:1008877
    DOI: 10.1371/journal.pgen.1008877
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    References listed on IDEAS

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    1. Laura M. Faure & Jean-Bernard Fiche & Leon Espinosa & Adrien Ducret & Vivek Anantharaman & Jennifer Luciano & Sébastien Lhospice & Salim T. Islam & Julie Tréguier & Mélanie Sotes & Erkin Kuru & Michae, 2016. "The mechanism of force transmission at bacterial focal adhesion complexes," Nature, Nature, vol. 539(7630), pages 530-535, November.
    2. Timothy S. Gardner & Charles R. Cantor & James J. Collins, 2000. "Construction of a genetic toggle switch in Escherichia coli," Nature, Nature, vol. 403(6767), pages 339-342, January.
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    Cited by:

    1. María Pérez-Burgos & Marco Herfurth & Andreas Kaczmarczyk & Andrea Harms & Katrin Huber & Urs Jenal & Timo Glatter & Lotte Søgaard-Andersen, 2024. "A deterministic, c-di-GMP-dependent program ensures the generation of phenotypically similar, symmetric daughter cells during cytokinesis," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Luís António Menezes Carreira & Dobromir Szadkowski & Stefano Lometto & Georg. K. A. Hochberg & Lotte Søgaard-Andersen, 2023. "Molecular basis and design principles of switchable front-rear polarity and directional migration in Myxococcus xanthus," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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