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Cited by 23Cellular Mechanics and InteractionsProtein Kinase Regulation and GTPase SignalingCellular transport and secretion

Excitable Rho dynamics control cell shape and motility by sequentially activating ERM proteins and actomyosin contractility

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Marshall-Burghardt, Seph, Migueles-Ramírez, Rodrigo A., Lin, Qiyao, El Baba, Nada, Saada, Rayan, Umar, Mustakim, Mavalwala, Kian, Hayer, Arnold·2024·Science Advances
DOI 10.1126/sciadv.adn6858PMC PMC11378911
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Abstract

Migration of endothelial and many other cells requires spatiotemporal regulation of protrusive and contractile cytoskeletal rearrangements that drive local cell shape changes. Unexpectedly, the small GTPase Rho, a crucial regulator of cell movement, has been reported to be active in both local cell protrusions and retractions, raising the question of how Rho activity can coordinate cell migration. Here, we show that Rho activity is absent in local protrusions and active during retractions. During retractions, Rho rapidly activated ezrin-radixin-moesin proteins (ERMs) to increase actin-membrane attachment, and, with a delay, nonmuscle myosin 2 (NM2). Rho activity was excitable, with NM2 acting as a slow negative feedback regulator. Strikingly, inhibition of SLK/LOK kinases, through which Rho activates ERMs, caused elongated cell morphologies, impaired Rho-induced cell contractions, and reverted Rho-induced blebbing. Together, our study demonstrates that Rho activity drives retractions by sequentially enhancing ERM-mediated actin-membrane attachment for force transmission and NM2-dependent contractility.

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Cited by

Sorted by citations

Authors
Marshall-Burghardt, S., Migueles-Ramírez, R. A., Lin, Q., El Baba, N., Saada, R., Umar, M., Mavalwala, K., & Hayer, A.
Affiliations
  • McGill University (CA)
  • Department of Biology, Stewart Biology Building, McGill University, Montréal, Québec H3A 1B1, Canada.
Corresponding author
Hayer, Arnold
ORCID
Venue
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Published
2024-09-06
Volume
10
Issue
36
Pages
eadn6858-eadn6858
ISSN
2375-2548 (ISSN-L)
DOI
10.1126/sciadv.adn6858
PMC
PMC11378911
OpenAlex
W4402294569
Cited by
23
References
3
Citations by year
2026: 12 · 2025: 8 · 2024: 3
FWCI
4.88
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Science Advances (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship@McGill (McGill) (submittedVersion)
  • McGill-DEV
Funders
  • McGill University (SCR_017697)
  • Canadian Institutes of Health Research
  • Natural Sciences and Engineering Research Council of Canada (rgpin-2018-05831, RGPIN 2018)
  • Fonds de recherche du Québec – Nature et technologies
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
Rho GTPases, cell migration, cell shape, cell protrusions, cell retraction, ezrin-radixin-moesin proteins, actomyosin contractility, blebbing, negative feedback regulation, endothelial cells
MeSH terms
Ezrin, Actins, Actomyosin, Animals, Cell Movement, Cytoskeletal Proteins, Humans, Membrane Proteins, Microfilament Proteins, rho GTP-Binding Proteins, Myosin Type II, Cell Shape

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