A lateral signalling pathway coordinates shape volatility during cell migration

Liang Zhang, Valbona Luga, Sarah K. Armitage, Martin Musiol, Amy Won, Christopher M. Yip, Sergey V. Plotnikov and Jeffrey L. Wrana ()
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Liang Zhang: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Valbona Luga: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Sarah K. Armitage: University of Toronto
Martin Musiol: University of Toronto
Amy Won: Institute of Biomaterials and Biomedical Engineering, The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
Christopher M. Yip: Institute of Biomaterials and Biomedical Engineering, The Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
Sergey V. Plotnikov: University of Toronto
Jeffrey L. Wrana: Center for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract Cell migration is fundamental for both physiological and pathological processes. Migrating cells usually display high dynamics in morphology, which is orchestrated by an integrative array of signalling pathways. Here we identify a novel pathway, we term lateral signalling, comprised of the planar cell polarity (PCP) protein Pk1 and the RhoGAPs, Arhgap21/23. We show that the Pk1–Arhgap21/23 complex inhibits RhoA, is localized on the non-protrusive lateral membrane cortex and its disruption leads to the disorganization of the actomyosin network and altered focal adhesion dynamics. Pk1-mediated lateral signalling confines protrusive activity and is regulated by Smurf2, an E3 ubiquitin ligase in the PCP pathway. Furthermore, we demonstrate that dynamic interplay between lateral and protrusive signalling generates cyclical fluctuations in cell shape that we quantify here as shape volatility, which strongly correlates with migration speed. These studies uncover a previously unrecognized lateral signalling pathway that coordinates shape volatility during productive cell migration.

Date: 2016
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DOI: 10.1038/ncomms11714

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