Nonmuscle myosin 2 without an assembly competence domain can incorporate into established filaments in cells

Myosin 2 dynamically assembles into filaments that exert force on the actin cytoskeleton. To form filaments, myosin 2 monomers transition between folded and unfolded states. Monomer unfolding exposes an extended coiled-coil that interacts with other monomers in parallel and antiparallel fashions, enabling bipolar filament formation. A C-terminal domain of the coiled-coil, termed assembly competence domain (ACD), has been repeatedly identified as necessary for filament assembly. Here, we revisit ACD contribution when full-length filaments are present. Nonmuscle myosin 2A lacking the ACD (∆ACD) initially appears diffuse, but triton extraction of cytosolic fraction reveals cytoskeletal association. Disruption of the folded monomer enhances the cytoskeletal fraction, while inhibition of endogenous filament assembly appears to reduce it. Finally, high-resolution imaging of endogenous and exogenous myosin 2 reveals highly coincident filamentous structures, suggesting that ∆ACD constructs coassemble with endogenous myosin 2A filaments. Our data demonstrate that while the ACD is required for de novo filament assembly, it is not required for monomers to recognize and associate with established filaments in cells. More broadly, this highlights the existence of distinct pathways governing how monomers participate in nascent filament assembly and how monomers recognize and associate with established filaments to maintain steady-state contractile networks.

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Publication Details

Journal
Molecular Biology of the Cell
Published
2025-06-11
DOI
https://doi.org/10.1091/mbc.e24-07-0287
Primary Topic
Cardiomyopathy and Myosin Studies
Type
article
Field-Weighted Citation Impact
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article

Nonmuscle myosin 2 without an assembly competence domain can incorporate into established filaments in cells

Hiral Patel, Melissa A. Quintanilla, Kehan Wu, Huini Wu et al.
Molecular Biology of the Cell
Cardiomyopathy and Myosin Studies
article

Nonmuscle myosin 2 without an assembly competence domain can incorporate into established filaments in cells

Hiral Patel, Melissa A. Quintanilla, Kehan Wu, Huini Wu, Vraj Patel, Stefano Sala, Sasha Demeulenaere, Margaret A. Bennett, Jordan R. Beach, Margaret E Utgaard
article en

Abstract

Myosin 2 dynamically assembles into filaments that exert force on the actin cytoskeleton. To form filaments, myosin 2 monomers transition between folded and unfolded states. Monomer unfolding exposes an extended coiled-coil that interacts with other monomers in parallel and antiparallel fashions, enabling bipolar filament formation. A C-terminal domain of the coiled-coil, termed assembly competence domain (ACD), has been repeatedly identified as necessary for filament assembly. Here, we revisit ACD contribution when full-length filaments are present. Nonmuscle myosin 2A lacking the ACD (∆ACD) initially appears diffuse, but triton extraction of cytosolic fraction reveals cytoskeletal association. Disruption of the folded monomer enhances the cytoskeletal fraction, while inhibition of endogenous filament assembly appears to reduce it. Finally, high-resolution imaging of endogenous and exogenous myosin 2 reveals highly coincident filamentous structures, suggesting that ∆ACD constructs coassemble with endogenous myosin 2A filaments. Our data demonstrate that while the ACD is required for de novo filament assembly, it is not required for monomers to recognize and associate with established filaments in cells. More broadly, this highlights the existence of distinct pathways governing how monomers participate in nascent filament assembly and how monomers recognize and associate with established filaments to maintain steady-state contractile networks.

Molecular Biology of the CellVol. 36(8)
Loyola University Chicago (US)
Openalex Percentile: Top 77%
Cardiomyopathy and Myosin Studies
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