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.
Authors
- Hiral Patel (ORCID: https://orcid.org/0000-0002-2216-6584)
- Melissa A. Quintanilla (ORCID: https://orcid.org/0000-0002-6044-9606)
- Kehan Wu (ORCID: https://orcid.org/0000-0001-6273-2029)
- Huini Wu (ORCID: https://orcid.org/0009-0000-2073-1458)
- Vraj Patel (ORCID: https://orcid.org/0000-0001-5982-7457)
- Stefano Sala (ORCID: https://orcid.org/0000-0003-3675-6849)
- Sasha Demeulenaere (ORCID: https://orcid.org/0000-0003-3750-7609)
- Margaret A. Bennett
- Jordan R. Beach (ORCID: https://orcid.org/0000-0003-0633-4928)
- Margaret E Utgaard
Institutions
- Loyola University Chicago (US)
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
- 0.00