GO:0017024 myosin I binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0017024 myosin I binding is a molecular function defined as binding to a class I myosin, whose heavy chains are single-headed, possess tails of various lengths, and do not self-associate into bipolar filaments.
• Class I myosins are monomeric, membrane-associated motors that link actin filaments to cellular membranes and generate force at membrane-cytoskeleton interfaces.
• Myosin I binding partners include membrane lipids, calmodulin, actin, and adaptor proteins such as Dock5, enabling roles in endocytosis, exocytosis, cell migration, and wound healing.
• The motor and light-chain-binding domains regulate myosin-I activity, and tail domains mediate cargo and membrane interactions.
• Dysregulation of myosin I binding is linked to diabetic wound healing defects and broader membrane-trafficking pathologies.
• CRISPR knockout, point-mutation, knock-in, and overexpression models are key tools for dissecting myosin I binding function in cells and organisms.
Description
GO:0017024 myosin I binding is a molecular function term describing the selective interaction of a protein with a class I myosin. Class I myosins are single-headed, monomeric motors that do not form bipolar filaments, distinguishing them from conventional myosins such as myosin II. Since the discovery of myosin I, these motors have been recognized as central players at the interface between actin filaments and cellular membranes. The term captures any binding event directed at a myosin I heavy chain, including interactions mediated by motor, neck, or tail domains. Researchers study myosin I binding because it underlies fundamental processes such as membrane trafficking, cell motility, and force generation at the plasma membrane. The binding function is not merely structural; it recruits myosin I to specific membrane compartments and regulates its motor activity in response to cellular signals. Understanding GO:0017024 therefore provides mechanistic insight into how cells couple actin dynamics to membrane remodeling, and how disruption of these interactions contributes to disease.
myosin I binding At A Glance
| GO ID | GO:0017024 |
|---|---|
| GO term | myosin I binding |
| Ontology | molecular_function |
| Synonym | none |
| Definition | Binding to a class I myosin; myosin I heavy chains are single-headed, possess tails of various lengths, and do not self-associate into bipolar filaments. |
| Major function | Mediates recruitment, regulation, and membrane association of class I myosins. |
| Representative binders | Calmodulin, membrane phospholipids, actin, Dock5, and other adaptors. |
| Cellular context | Actin-membrane interfaces, endocytic and exocytic sites, cell cortex. |
| Research relevance | Links actin dynamics to membrane trafficking, cell migration, and disease processes such as impaired wound healing. |
What Is GO:0017024?
In our own words, GO:0017024 myosin I binding describes the ability of a protein or molecule to physically associate with a class I myosin. Class I myosins are defined by a single heavy chain that is single-headed, has a tail of variable length, and does not self-associate into bipolar filaments. This binding can occur through the motor domain, the light-chain-binding neck region, or the tail, and it often serves to localize myosin I to membranes or to regulate its activity.
Why Is myosin I binding Important in Cell Biology?
Myosin I binding is important because class I myosins are the primary motors that connect actin filaments to cellular membranes, and their binding partners determine where and when force is generated. This function is essential for endocytosis, exocytosis, cell migration, and membrane tension regulation. Defects in myosin I binding have been implicated in human disease, including diabetic wound healing, where Myo1c and Dock5 interactions are critical. Thus, GO:0017024 provides a mechanistic entry point for understanding membrane-cytoskeleton coupling in health and disease.
• Controls recruitment of class I myosins to membranes, enabling force generation at the cell cortex.
• Regulates endocytic and exocytic trafficking through actin-membrane coupling.
• Supports cell migration and polarized growth by organizing membrane protrusions.
• Mediates calcium-dependent regulation via calmodulin binding to the myosin I neck.
• Facilitates membrane lipid association through tail-domain phospholipid binding.
• Is required for efficient diabetic wound healing via Myo1c/Dock5 signaling.
• Provides a target for studying motor regulation by the motor and light-chain-binding domains.
• Offers a paradigm for understanding monomeric myosin function distinct from bipolar myosin II.
• Links actin dynamics to membrane remodeling in diverse cell types.
• Represents a molecular function that can be systematically dissected using CRISPR models.
What Happens During myosin I binding?
Membrane recruitment of myosin I
In simple terms: Myosin I binds to membrane lipids, which helps it attach to the cell surface.
Class I myosins can bind directly to phospholipid vesicles and membrane lipids, localizing the motor to cellular membranes. This binding is mediated in part by the tail domain and is regulated by calcium and calmodulin. Membrane association is a prerequisite for myosin I to generate force at the membrane-cytoskeleton interface.
Calmodulin and light-chain regulation
In simple terms: Calmodulin acts as a light chain that controls myosin I activity.
Brush border myosin I has a calmodulin/phosphatidylserine switch, and calmodulin binding to the neck region regulates motor activity. The light-chain-binding domain is a key regulatory module that tunes myosin-I function in response to calcium signals.
Actin engagement and force generation
In simple terms: Once bound to membranes, myosin I pulls on actin filaments to produce force.
Membrane-associated myosin-I generates force against actin filaments, contributing to membrane tension and deformation. The motor domain hydrolyzes ATP to drive movement along actin, while tail interactions anchor the motor to membranes.
Adaptor-mediated targeting
In simple terms: Other proteins help bring myosin I to specific locations.
Adaptor proteins such as Dock5 interact with Myo1c to promote diabetic wound healing, illustrating how binding partners target myosin I to specific cellular tasks. Such adaptors expand the functional repertoire of myosin I beyond direct lipid binding.
Key Genes Involved in GO:0017024 myosin I binding
The following genes and proteins are experimentally implicated in myosin I binding or its regulation, based on the cited literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| MYO1C | Class I myosin heavy chain; binds membranes and actin | Implicated in diabetic wound healing via Dock5 interaction |
| MYO1A | Brush border myosin I heavy chain | Model for calmodulin/phosphatidylserine regulation and tail actin binding |
| MYO1B | Class I myosin heavy chain | Studied for motor and light-chain domain regulation |
| MYO1E | Class I myosin heavy chain | Involved in membrane trafficking and force generation |
| MYO1F | Class I myosin heavy chain | Potential roles in immune cell motility |
| MYO1G | Class I myosin heavy chain | Studied in membrane-cytoskeleton coupling |
| CALM1 | Calmodulin light chain | Regulates myosin I activity via calcium-dependent binding |
| CALM2 | Calmodulin light chain | Alternative calmodulin isoform for myosin I regulation |
| CALM3 | Calmodulin light chain | Contributes to myosin I light-chain regulation |
| DOCK5 | Adaptor protein | Interacts with Myo1c to promote wound healing |
| ACTB | Actin filament subunit | Substrate for myosin I motor activity |
| ACTG1 | Actin filament subunit | Cytoskeletal track for myosin I |
| PS | Phosphatidylserine lipid | Membrane binding partner for myosin I |
| PI | Phosphoinositide lipids | Membrane lipids that bind myosin I |
| ATP | Energy source | Required for myosin I motor function |
| Ca2+ | Signaling ion | Regulates calmodulin and myosin I binding |
How Is myosin I binding Regulated?
Myosin I binding is regulated by calcium signaling through calmodulin, which associates with the light-chain-binding domain and modulates motor activity. Phosphatidylserine and other membrane lipids also influence binding, acting as a switch for membrane association. The motor domain and light-chain-binding domain together control myosin-I regulation and cargo interactions. Additionally, adaptor proteins such as Dock5 can regulate myosin I function in specific contexts like wound healing.
myosin I binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| MYO1C | Diabetic wound healing | Knockout and knock-in models in diabetic mice |
| DOCK5 | Diabetic wound healing | Overexpression and knockout in keratinocytes |
| MYO1A | Brush border function | Point-mutation models for calmodulin binding |
| MYO1B | Membrane trafficking | Knockout in cultured cells |
| MYO1E | Force generation | Tagged knock-in for live imaging |
Diabetic wound healing
Liraglutide promotes diabetic wound healing via the Myo1c/Dock5 axis, linking myosin I binding to a clinically relevant repair process. Disruption of this interaction impairs healing, suggesting that myosin I binding is a therapeutic target.
Membrane trafficking disorders
Because class I myosins mediate endocytosis and exocytosis, defects in myosin I binding can contribute to trafficking-related pathologies. The motor and light-chain domains are critical for these functions.
Cell migration and cancer
Myosin I binding supports cell migration by coupling actin to membranes, a process hijacked in cancer metastasis. Force generation by membrane-associated myosin-I is directly relevant to invasive behavior.
From myosin I binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of myosin I binding impair wound healing? | MYO1C knockout mouse |
| How does calmodulin regulate myosin I? | Point mutation in MYO1A neck domain |
| Where does myosin I localize in live cells? | Tagged knock-in of MYO1C |
| Can overexpression rescue binding defects? | MYO1C overexpression |
| What adaptors mediate myosin I targeting? | DOCK5 knockout |
| How does membrane lipid binding affect motor activity? | In vitro liposome assays with purified myosin I |
How to Study the myosin I binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Liposome co-sedimentation | Membrane lipid binding | Assessing myosin I tail-lipid interactions |
| Actin co-sedimentation | Actin binding | Measuring motor domain affinity |
| Live-cell fluorescence | Subcellular localization | Tracking myosin I dynamics |
| Co-immunoprecipitation | Protein-protein interactions | Identifying binding partners |
| Mass spectrometry | Interactome composition | Discovering novel binders |
| CRISPR knockout | Loss-of-function phenotype | Testing causal roles |
| CRISPR knock-in | Tagged protein expression | Imaging and pulldown |
Biochemical binding assays
Liposome co-sedimentation and actin-binding assays can measure direct binding of myosin I to membranes and actin. These methods are foundational for defining GO:0017024 activity.
Live-cell imaging
Tagged knock-in of myosin I allows visualization of dynamic membrane association and force generation in living cells. Fluorescence microscopy reveals localization at endocytic and exocytic sites.
Proteomics and interactomics
Affinity purification coupled to mass spectrometry can identify novel myosin I binding partners, expanding the network beyond known adaptors like Dock5.
Genetic perturbation
CRISPR knockout and point-mutation models enable causal testing of myosin I binding in processes such as wound healing and trafficking.
How CRISPR Can Be Used to Study GO:0017024 myosin I binding
Knockout
CRISPR knockout of MYO1C or DOCK5 can abolish myosin I binding and reveal its requirement in wound healing and trafficking. Knockout models are essential for loss-of-function studies of GO:0017024.
Point Mutation
Point mutations in the calmodulin-binding neck of MYO1A can dissect the calmodulin/phosphatidylserine switch that regulates myosin I binding. Such models test specific residues without deleting the entire protein.
Knock-in
Knock-in of fluorescent tags into MYO1C enables real-time imaging of myosin I binding and force generation at membranes. This approach preserves endogenous regulation.
Overexpression
Overexpression of MYO1C or DOCK5 can rescue binding defects and enhance wound healing in diabetic models. Overexpression is useful for gain-of-function studies of myosin I binding.
How EDITGENE Supports myosin I binding Research
Researchers studying myosin I binding-related genes often need to determine whether a candidate gene is causally involved in membrane-cytoskeleton coupling, trafficking, or disease phenotypes. EDITGENE provides the CRISPR tools and services to build precisely engineered cell and animal models for GO:0017024 research.
Contact EDITGENE today to design your custom CRISPR model for myosin I binding research.
Frequently Asked Questions About myosin I binding
What is myosin I binding?
Myosin I binding (GO:0017024) is the molecular function of selectively interacting with a class I myosin, a single-headed motor that does not form bipolar filaments.
What genes are involved in myosin I binding?
Key genes include MYO1C, MYO1A, MYO1B, MYO1E, MYO1F, MYO1G, CALM1-3, and DOCK5, based on published studies.
What is the GO ID for myosin I binding?
The GO ID is GO:0017024.
How is myosin I binding regulated?
It is regulated by calcium-calmodulin and membrane lipids such as phosphatidylserine, as well as by motor and light-chain domain interactions.
What diseases are linked to myosin I binding?
Diabetic wound healing defects are linked to Myo1c/Dock5 interactions, and broader trafficking and migration disorders are implicated.
What experimental models study myosin I binding?
Knockout, point-mutation, knock-in, and overexpression models in cells and mice are commonly used.
How does myosin I bind to membranes?
The tail domain binds phospholipids such as phosphatidylserine and phosphoinositides, localizing myosin I to membranes.
What is the role of calmodulin in myosin I binding?
Calmodulin acts as a light chain that binds the neck region and regulates myosin I activity in a calcium-dependent manner.
Can CRISPR be used to study myosin I binding?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression are all applicable to myosin I binding research.
Why is myosin I binding important for cell migration?
It couples actin filaments to membranes, generating force that drives membrane protrusion and cell movement.
Conclusion
GO:0017024 myosin I binding is a fundamental molecular function that connects actin dynamics to cellular membranes through class I myosins. Its regulation by calmodulin, lipids, and adaptors such as Dock5 positions it at the center of trafficking, migration, and wound healing. Continued research using CRISPR models will clarify how myosin I binding contributes to health and disease, and may reveal new therapeutic opportunities.
References
- 1. Coluccio LM. 1997. Myosin I.. Am J Physiol 273(2 Pt 1):C347-59 PMID: 9277333
- 2. Greenberg MJ et al.. 2013. Regulation and control of myosin-I by the motor and light chain-binding domains.. Trends Cell Biol 23(2):81-9 PMID: 23200340
- 3. Zhang Q et al.. 2024. Liraglutide Promotes Diabetic Wound Healing via Myo1c/Dock5.. Adv Sci (Weinh) 11(39):e2405987 PMID: 39159301
- 4. Oosawa F. 2018. Discovery of myosin I and Pollard-san.. Biophys Rev 10(6):1481-1482 PMID: 30446945
- 5. Swanljung-Collins H et al.. 1994. Brush border myosin I has a calmodulin/phosphatidylserine switch and tail actin-binding.. Adv Exp Med Biol 358:205-13 PMID: 7801806
- 6. Hayden SM et al.. 1990. Binding of brush border myosin I to phospholipid vesicles.. J Cell Biol 111(2):443-51 PMID: 2143194
- 7. Adams RJ et al.. 1989. Binding of myosin I to membrane lipids.. Nature 340(6234):565-8 PMID: 2770861
- 8. Pyrpassopoulos S et al.. 2016. Force Generation by Membrane-Associated Myosin-I.. Sci Rep 6:25524 PMID: 27156719
