GO:0097513 myosin II filament: Components, Assembly and Research Methods, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0097513 myosin II filament is a cellular component defined as a bipolar filament composed of myosin II molecules.
• Myosin II filaments assemble from myosin II monomers and are central to actomyosin contractility in processes such as cytokinesis, cell migration, and tissue morphogenesis.
• Myosin II filament dynamics include rapid assembly and disassembly (filament evanescence) that is regulated by phosphorylation and mechanical cues.
• Myosin II filament stacks can self-organize over long ranges to produce coordinated contractile forces.
• Dysregulation of myosin II filaments is linked to cancer therapy resistance, particularly in melanoma, and to smooth muscle dysfunction.
• CRISPR-based models (knockout, point mutation, knock-in, overexpression) enable causal interrogation of myosin II filament components and regulators.
Description
The myosin II filament (GO:0097513) is a cellular component defined as a bipolar filament composed of myosin II molecules. Myosin II is a non-processive motor protein that assembles into bipolar filaments, which interact with actin filaments to generate contractile forces essential for cytokinesis, cell migration, and tissue morphogenesis. Unlike muscle myosin, non-muscle myosin II dynamically assembles and disassembles, a property termed filament evanescence, which allows rapid remodeling of the actomyosin cytoskeleton. The myosin II filament is therefore a key structural and functional unit in cell biology, and its study spans biochemistry, biophysics, and disease research. Understanding its assembly, regulation, and roles in disease is critical for developing targeted therapies, as highlighted by studies linking myosin II reactivation to melanoma therapy resistance.
myosin II filament At A Glance
| GO ID | GO:0097513 |
|---|---|
| GO term | myosin II filament |
| Ontology | cellular_component |
| Synonym | None |
| Major function | Bipolar filament composed of myosin II molecules that generates contractile forces with actin |
| Assembly | Myosin II monomers assemble into bipolar filaments; dynamic assembly/disassembly (evanescence) |
| Regulation | Phosphorylation of myosin regulatory light chain and mechanical cues |
| Disease relevance | Cancer therapy resistance, smooth muscle dysfunction |
What Is GO:0097513?
GO:0097513 myosin II filament is a cellular component consisting of a bipolar filament composed of myosin II molecules. This structure serves as the functional unit of myosin II motor activity, enabling the generation of contractile forces through interaction with actin filaments.
Why Is myosin II filament Important in Cell Biology?
The myosin II filament is essential for fundamental cellular processes including cytokinesis, cell migration, and tissue morphogenesis. Its dynamic assembly and disassembly allow cells to rapidly reorganize the actomyosin cytoskeleton in response to mechanical and biochemical signals. Dysregulation of myosin II filaments contributes to human diseases such as cancer therapy resistance and smooth muscle disorders. Therefore, understanding myosin II filament biology is crucial for both basic research and therapeutic development.
• Drives cytokinesis by forming the contractile ring.
• Enables cell migration and tissue morphogenesis through actomyosin contractility.
• Exhibits dynamic assembly/disassembly (evanescence) critical for smooth muscle function.
• Self-organizes into stacks for long-range force generation.
• Linked to melanoma therapy resistance via myosin II reactivation.
• Regulated by mechanical cues from the extracellular matrix.
• Target for CRISPR-based functional studies of contractility genes.
• Involved in mechanotransduction and stem cell lineage specification.
• Potential therapeutic target in cancer and smooth muscle disorders.
• Studied using advanced imaging techniques like interferometric scattering microscopy.
Structure and Composition of myosin II filament
Myosin II monomers and bipolar filament assembly
In simple terms: Myosin II molecules stick together to form a tiny bipolar (two-ended) filament.
Myosin II monomers consist of two heavy chains, two regulatory light chains, and two essential light chains. These monomers assemble into bipolar filaments through interactions between their coiled-coil tails, while the globular heads project outward to interact with actin. The bipolar arrangement allows the filament to pull actin filaments in opposite directions, generating contraction.
Filament evanescence and dynamics
In simple terms: Myosin II filaments can quickly fall apart and reform, which helps cells change shape and move.
Myosin II filaments are dynamic structures that undergo constant assembly and disassembly, a process known as filament evanescence. This dynamic behavior is crucial for smooth muscle function and allows rapid remodeling of the cytoskeleton. Interferometric scattering microscopy has revealed that myosin II filament dynamics in actin networks involve rapid turnover.
Actomyosin contractile ring in cytokinesis
In simple terms: During cell division, myosin II filaments form a ring that pinches the cell in two.
During cytokinesis, myosin II filaments assemble into a contractile ring with actin filaments. Ultrastructural analysis has shown that actomyosin filaments in the contractile ring are highly organized and dynamic, ensuring proper cell division. This ring constricts to divide the cell, a process dependent on myosin II motor activity.
Long-range self-organization of myosin II filament stacks
In simple terms: Myosin II filaments can stack together over long distances to produce coordinated pulling forces.
Myosin II filaments can self-organize into stacks that span long distances, enabling coordinated force generation across cells. This long-range self-organization is important for tissue-scale contractility and morphogenesis.
Regulation by phosphorylation and mechanical cues
In simple terms: Chemical tags and physical forces control how myosin II filaments assemble and work.
Phosphorylation of the myosin regulatory light chain promotes filament assembly and activation. Additionally, mechanical cues from the extracellular matrix, such as stiffness, direct stem cell lineage specification through actomyosin contractility. Matrix elasticity influences myosin II filament organization and function.
Key Genes Involved in GO:0097513 myosin II filament
The following genes and proteins are key components or regulators of myosin II filaments, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| MYH9 | Non-muscle myosin II heavy chain; forms bipolar filaments | Mutations cause MYH9-related disorders; studied in cell motility |
| MYH10 | Non-muscle myosin II heavy chain; involved in cytokinesis | Knockout leads to cytokinesis defects |
| MYH11 | Smooth muscle myosin heavy chain; filament formation | Mutations linked to aortic aneurysms |
| MYL9 | Myosin regulatory light chain; regulates filament assembly | Phosphorylation controls contractility |
| MYL12A | Myosin regulatory light chain; modulates motor activity | Regulates smooth muscle contraction |
| MYL12B | Myosin regulatory light chain; modulates motor activity | Regulates smooth muscle contraction |
| MYL6 | Essential light chain; stabilizes myosin structure | Component of myosin II holoenzyme |
| ROCK1 | Kinase that phosphorylates myosin light chain | Regulates myosin II filament assembly |
| ROCK2 | Kinase that phosphorylates myosin light chain | Regulates myosin II filament assembly |
| MYLK | Myosin light chain kinase; activates myosin II | Phosphorylates regulatory light chain |
| PPP1R12A | Myosin phosphatase regulatory subunit; dephosphorylates myosin | Controls filament disassembly |
| ACTB | Beta-actin; forms actin filaments interacting with myosin II | Essential for actomyosin contractility |
| ACTG1 | Gamma-actin; forms actin filaments | Component of actomyosin cytoskeleton |
| TPM1 | Tropomyosin; stabilizes actin filaments | Regulates myosin II binding |
| CTTN | Cortactin; regulates actin dynamics | Modulates actomyosin assembly |
| VCL | Vinculin; links actin to focal adhesions | Mechanotransduction |
| TLN1 | Talin; connects integrins to actin | Mechanotransduction |
| ZYX | Zyxin; focal adhesion protein | Mechanotransduction |
How Is myosin II filament Regulated?
Myosin II filament assembly and activity are regulated by phosphorylation of the myosin regulatory light chain, primarily by ROCK and MYLK, and by dephosphorylation via myosin phosphatase. Mechanical cues from the extracellular matrix, such as stiffness, also regulate myosin II filament organization and contractility, influencing stem cell lineage specification. Additionally, filament evanescence is modulated by interactions with actin networks and associated proteins.
myosin II filament and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| MYH9 | MYH9-related disorders (thrombocytopenia, hearing loss) | Knockout or point mutation in cell lines |
| MYH11 | Aortic aneurysm, patent ductus arteriosus | Knock-in of patient mutations in smooth muscle cells |
| MYH10 | Cytokinesis defects, cancer | Knockout in cancer cell lines |
| ROCK1 | Cancer, smooth muscle disorders | Knockout or overexpression in melanoma cells |
| MYLK | Asthma, smooth muscle dysfunction | Point mutation knock-in in airway smooth muscle cells |
Myosin II filaments in cancer therapy resistance
Myosin II reactivation and cytoskeletal remodeling are hallmarks of melanoma therapy resistance. In melanoma, increased myosin II filament assembly and contractility contribute to resistance against targeted therapies, making myosin II a potential therapeutic vulnerability. Targeting myosin II filaments could overcome resistance in melanoma patients.
Myosin II filaments in smooth muscle dysfunction
Filament evanescence of myosin II is critical for smooth muscle function. Dysregulation of myosin II filament dynamics can lead to smooth muscle disorders, including hypertension and asthma. Mutations in MYH11, a smooth muscle myosin heavy chain, are associated with aortic aneurysms and patent ductus arteriosus.
Myosin II filaments in mechanotransduction and stem cell fate
Matrix elasticity directs stem cell lineage specification through actomyosin contractility. Myosin II filaments sense mechanical cues from the extracellular matrix, and their activity influences whether stem cells differentiate into bone, muscle, or neuronal lineages. This has implications for regenerative medicine and tissue engineering.
From myosin II filament-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does MYH9 knockout disrupt myosin II filament assembly? | MYH9 knockout cell line (e.g., HeLa) |
| How does MYH11 point mutation affect smooth muscle contractility? | MYH11 point mutation knock-in in smooth muscle cells |
| Can overexpression of MYL9 rescue filament dynamics? | MYL9 overexpression in knockout background |
| What is the role of ROCK1 in melanoma therapy resistance? | ROCK1 knockout or overexpression in melanoma cells |
| How does matrix stiffness affect myosin II filament organization? | Stem cells cultured on tunable stiffness hydrogels |
| Does tagged MYH10 knock-in reveal filament dynamics? | Tagged MYH10 knock-in cell line for live imaging |
How to Study the myosin II filament Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Interferometric scattering microscopy | Myosin II filament dynamics in actin networks | Live-cell imaging of filament turnover |
| Fluorescence microscopy | Localization and assembly of myosin II filaments | Cytokinesis and cell migration studies |
| Electron microscopy | Ultrastructure of actomyosin filaments | Contractile ring organization |
| In vitro assembly assay | Filament formation and ATPase activity | Biochemical dissection of assembly |
| CRISPR knockout screening | Genes regulating myosin II filament function | Cancer therapy resistance |
| Phosphorylation assays | Regulatory light chain phosphorylation | Regulation of filament assembly |
| Traction force microscopy | Contractile forces generated by myosin II | Mechanotransduction studies |
| RNA-seq | Transcriptional changes in myosin II-related genes | Pathway analysis |
Live-cell imaging of myosin II filaments
Interferometric scattering microscopy and fluorescence microscopy enable real-time visualization of myosin II filament dynamics in actin networks. These techniques reveal assembly, disassembly, and movement of individual filaments.
Ultrastructural analysis of actomyosin filaments
Electron microscopy, including ultrastructural analysis, provides high-resolution views of myosin II filament organization in the contractile ring during cytokinesis. This method reveals filament length, orientation, and packing.
Biochemical assays for filament assembly
In vitro assembly assays using purified myosin II and actin measure filament formation, ATPase activity, and contractility. These assays help dissect the roles of regulatory light chain phosphorylation.
CRISPR screening for regulators of myosin II filaments
Genome-wide CRISPR knockout screens can identify genes that regulate myosin II filament assembly and function, as demonstrated in melanoma therapy resistance studies. Bioinformatics analysis of screening data reveals pathways and networks.
How CRISPR Can Be Used to Study GO:0097513 myosin II filament
Knockout
CRISPR knockout of myosin II heavy chain genes (e.g., MYH9, MYH10) disrupts filament assembly and contractility, enabling studies of cytokinesis and migration. Knockout of regulators like ROCK1 reveals their role in filament dynamics.
Point Mutation
Point mutations in MYH11 or MYL9 can be introduced to model patient-specific variants that affect filament assembly or regulation. These models help dissect the molecular basis of smooth muscle disorders.
Knock-in
Knock-in of tagged myosin II (e.g., GFP-MYH10) allows live-cell imaging of filament dynamics. Knock-in of disease-associated mutations provides physiologically relevant models.
Overexpression
Overexpression of myosin II components or regulators (e.g., MYL9, ROCK1) can enhance filament assembly and contractility, useful for studying gain-of-function effects in cancer.
How EDITGENE Supports myosin II filament Research
Researchers studying myosin II filament-related genes often need to determine whether a candidate gene is causally involved in filament assembly, regulation, or disease. EDITGENE provides comprehensive CRISPR services to enable such functional studies.
Contact EDITGENE today to design your custom CRISPR model for myosin II filament research.
Frequently Asked Questions About myosin II filament
What is GO:0097513 myosin II filament?
GO:0097513 is a cellular component defined as a bipolar filament composed of myosin II molecules.
What genes are involved in myosin II filament assembly?
Key genes include MYH9, MYH10, MYH11, MYL9, MYL12A, MYL12B, ROCK1, ROCK2, and MYLK.
How is myosin II filament regulated?
It is regulated by phosphorylation of the myosin regulatory light chain by ROCK and MYLK, and by mechanical cues.
What diseases are associated with myosin II filaments?
They are linked to cancer therapy resistance, smooth muscle disorders, and MYH9-related diseases.
What methods are used to study myosin II filaments?
Live-cell imaging, electron microscopy, in vitro assembly assays, and CRISPR screening.
Can CRISPR be used to study myosin II filaments?
Yes, knockout, point mutation, knock-in, and overexpression models enable functional studies.
What is filament evanescence?
It is the dynamic assembly and disassembly of myosin II filaments, critical for smooth muscle function.
How do myosin II filaments generate force?
They interact with actin filaments via their motor heads, pulling actin in opposite directions due to their bipolar structure.
What is the role of myosin II filaments in cytokinesis?
They form the contractile ring that pinches the cell during division.
Are there EDITGENE services for myosin II filament research?
Yes, EDITGENE offers knockout, point mutation, knock-in, overexpression, library screening, and bioinformatics services.
Conclusion
The myosin II filament (GO:0097513) is a dynamic bipolar structure essential for actomyosin contractility in processes ranging from cytokinesis to tissue morphogenesis. Its regulation by phosphorylation and mechanical cues, and its implication in cancer and smooth muscle diseases, make it a compelling research target. CRISPR-based models and advanced imaging techniques continue to unravel its complex biology. EDITGENE provides the tools to accelerate discoveries in this field.
References
- 1. Wang L et al.. 2021. Filament evanescence of myosin II and smooth muscle function.. J Gen Physiol 153(3) PMID: 33606000
- 2. Engler AJ et al.. 2006. Matrix elasticity directs stem cell lineage specification.. Cell 126(4):677-89 PMID: 16923388
- 3. Svitkina T. 2018. The Actin Cytoskeleton and Actin-Based Motility.. Cold Spring Harb Perspect Biol 10(1) PMID: 29295889
- 4. Fenix AM et al.. 2018. Assembly of myosin II filament arrays: Network Contraction versus Expansion.. Cytoskeleton (Hoboken) 75(12):545-549 PMID: 30126071
- 5. Arima T et al.. 2023. Dynamics of actomyosin filaments in the contractile ring revealed by ultrastructural analysis.. Genes Cells 28(12):845-856 PMID: 37844904
- 6. Mosby LS et al.. 2020. Myosin II Filament Dynamics in Actin Networks Revealed with Interferometric Scattering Microscopy.. Biophys J 118(8):1946-1957 PMID: 32191863
- 7. Orgaz JL et al.. 2020. Myosin II Reactivation and Cytoskeletal Remodeling as a Hallmark and a Vulnerability in Melanoma Therapy Resistance.. Cancer Cell 37(1):85-103.e9 PMID: 31935375
- 8. Hu S et al.. 2017. Long-range self-organization of cytoskeletal myosin II filament stacks.. Nat Cell Biol 19(2):133-141 PMID: 28114270
