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A lateral signalling pathway coordinates shape volatility during cell migration.

TitleA lateral signalling pathway coordinates shape volatility during cell migration.
Publication TypeJournal Article
Year of Publication2016
AuthorsZhang L, Luga V, Armitage SK, Musiol M, Won A, Yip CM, Plotnikov SV, Wrana JL
JournalNat Commun
Volume7
Pagination11714
Date Published2016
ISSN2041-1723
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.

DOI10.1038/ncomms11714
Alternate JournalNat Commun
PubMed ID27226243

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