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Cited by 33Cellular Mechanics and InteractionsProtein Kinase Regulation and GTPase SignalingCardiomyopathy and Myosin Studies

Tyrosine Phosphorylation of the Myosin Regulatory Light Chain Controls Non-muscle Myosin II Assembly and Function in Migrating Cells

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Aguilar-Cuenca, Rocío, Llorente-González, Clara, Chapman, Jessica R., Talayero, Vanessa C., Garrido-Casado, Marina, Delgado-Arévalo, Cristina, Millán-Salanova, María, Shabanowitz, Jeffrey +4 more·2020·Current Biology
DOI 10.1016/j.cub.2020.04.057PMC PMC7343590
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Abstract

Active non-muscle myosin II (NMII) enables migratory cell polarization and controls dynamic cellular processes, such as focal adhesion formation and turnover and cell division. Filament assembly and force generation depend on NMII activation through the phosphorylation of Ser19 of the regulatory light chain (RLC). Here, we identify amino acid Tyr (Y) 155 of the RLC as a novel regulatory site that spatially controls NMII function. We show that Y155 is phosphorylated in vitro by the Tyr kinase domain of epidermal growth factor (EGF) receptor. In cells, phosphorylation of Y155, or its phospho-mimetic mutation (Glu), prevents the interaction of RLC with the myosin heavy chain (MHCII) to form functional NMII units. Conversely, Y155 mutation to a structurally similar but non-phosphorylatable amino acid (Phe) restores the more dynamic cellular functions of NMII, such as myosin filament formation and nascent adhesion assembly, but not those requiring stable actomyosin bundles, e.g., focal adhesion elongation or migratory front-back polarization. In live cells, phospho-Y155 RLC is prominently featured in protrusions, where it prevents NMII assembly. Our data indicate that Y155 phosphorylation constitutes a novel regulatory mechanism that contributes to the compartmentalization of NMII assembly and function in live cells.

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Cited by

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Authors
Aguilar-Cuenca, R., Llorente-González, C., Chapman, J. R., Talayero, V. C., Garrido-Casado, M., Delgado-Arévalo, C., Millán-Salanova, M., Shabanowitz, J., Hunt, D. F., Sellers, J. R., Heissler, S. M., & Vicente-Manzanares, M.
Affiliations
  • Hospital Universitario de La Princesa (ES)
  • Consejo Superior de Investigaciones Científicas (ES)
  • University of Virginia (US)
  • National Institutes of Health (US)
  • The Ohio State University Wexner Medical Center (US)
ORCID
Venue
Current Biology
Publisher
Elsevier BV
Published
2020-07
Volume
30
Issue
13
Pages
2446-2458.e6
ISSN
0960-9822 (ISSN-L)
DOI
10.1016/j.cub.2020.04.057
PMC
PMC7343590
OpenAlex
W3033485736
Cited by
33
References
0
Citations by year
2026: 3 · 2025: 8 · 2024: 7 · 2023: 1 · 2022: 6 · 2021: 6 · 2020: 2
FWCI
1.85
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
Funders
  • Fundación BBVA (IDEAS-VICE18, 14-BBM-340)
  • National Institutes of Health (GM 037537, K22HL131869)
  • Junta de Castilla y León (CLC\u20132017\u201301)
  • National Heart, Lung, and Blood Institute
  • Fundación Ramón Areces
  • Ministerio de Economía y Competitividad (CIVP16A1831, SAF2017-87408-R, SAF2014-54705-R)
  • Consejería de Educación, Junta de Castilla y León
  • Fundación Científica Asociación Española Contra el Cáncer
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
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
Keywords
non-muscle myosin II, myosin regulatory light chain, tyrosine phosphorylation, EGF receptor tyrosine kinase, myosin heavy chain, myosin filament assembly, cell migration, focal adhesion formation, cell polarization, actomyosin, protrusions
MeSH terms
A549 Cells, Animals, Cell Movement, Cricetulus, Humans, Phosphorylation, Tyrosine, CHO Cells, Spodoptera, Myosin Light Chains, Myosin Type II, HEK293 Cells, Sf9 Cells

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