{"gene":"MYO10","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":2006,"finding":"Full-length Myo10 (with motor domain) localizes to filopodial tips and undergoes intrafilopodial motility in neuronal CAD cells, while headless Myo10 (lacking the motor domain) does not localize to filopodial tips and does not undergo intrafilopodial motility, demonstrating the motor domain is necessary for these activities.","method":"Live cell imaging of GFP-tagged full-length vs. headless Myo10 constructs in transfected CAD neuronal cells","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct live-cell imaging with domain-deletion constructs in a neuronal model, replicated finding consistent with multiple studies","pmids":["16371656"],"is_preprint":false},{"year":2006,"finding":"Brain expresses a headless isoform of Myo10 that lacks the myosin head (motor) domain but retains three PH domains, a MyTH4 domain, and a FERM domain; both full-length and headless Myo10 are developmentally regulated in mouse brain.","method":"Immunoblotting and immunofluorescence of mouse brain tissue and CAD cells; GFP-construct transfection","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (immunoblot, immunofluorescence, functional GFP constructs) in a single focused study","pmids":["16371656"],"is_preprint":false},{"year":2013,"finding":"Myo10 promotes tunneling nanotube (TNT) formation in neuronal CAD cells; both the motor domain and the tail domain are required, with the F2 lobe of the FERM domain within the tail specifically necessary for TNT formation, independent of integrin and N-cadherin binding.","method":"Overexpression and domain-deletion/mutation constructs in CAD cells; quantification of TNT number and vesicle transfer","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Moderate — domain-deletion analysis with functional readout (TNT number, vesicle transfer), single lab with multiple constructs","pmids":["23886947"],"is_preprint":false},{"year":2012,"finding":"Recruitment of Myo10 to phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) via its PH domain is essential for axon formation; Myo10 knockdown impairs axon outgrowth, and ectopic expression of Myo10 mutants induces multiple axon-like neurites in a motor-independent manner.","method":"RNAi knockdown, EGFP-tagged Myo10 mutant overexpression in hippocampal neurons; immunofluorescence with Tau-1 and Tuj1 markers; in vivo neuronal migration assay in developing neocortex","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 / Moderate — loss-of-function and gain-of-function with domain mutants, both in vitro and in vivo validation","pmids":["22590642"],"is_preprint":false},{"year":2017,"finding":"Myo10 knockout macrophages display markedly reduced filopodia formation but have normal morphology, motility, and phagocytic cup formation, placing Myo10 downstream of Cdc42 specifically in filopodia induction rather than general macrophage morphology or phagocytosis.","method":"Myo10 knockout mice; spinning disk confocal live-cell imaging of Lifeact-EGFP macrophages; phagocytosis assays with E. coli and zymosan particles","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic knockout with multiple orthogonal functional readouts (filopodia quantification, phagocytosis assays, live imaging)","pmids":["28289096"],"is_preprint":false},{"year":2014,"finding":"Myo10 knockdown in NLT neuronal cells impairs cell motility, disrupts cell polarity (random orientation of Golgi), and decreases cell-matrix adhesion; N-cadherin expression rescues the migration deficiency caused by Myo10 knockdown, indicating Myo10 promotes neurogenic cell migration through N-cadherin-mediated cell adhesion.","method":"shRNA knockdown in NLT cells; wound healing assay with Golgi staining for polarity; cell-matrix adhesion assay; N-cadherin rescue in cell aggregate and collagen gel assays","journal":"In vitro cellular & developmental biology. Animal","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab, loss-of-function with rescue experiment, but limited mechanistic depth","pmids":["25491426"],"is_preprint":false},{"year":2019,"finding":"Full-length (motorized) Myo10 is required for normal prenatal development (neural tube closure, digit formation) and postnatal hyaloid vasculature regression in mice; the headless Myo10 isoform does not induce filopodia but localizes strongly to the plasma membrane independent of the MyTH4-FERM domain.","method":"Myo10tm2 reporter knockout mice lacking full-length but not headless Myo10; MRI of brain, retinal whole-mount preparations; in vitro filopodia assays with headless Myo10","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 2 / Moderate — isoform-specific knockout mouse with multiple orthogonal phenotypic readouts plus in vitro domain localization studies","pmids":["30679680"],"is_preprint":false},{"year":2021,"finding":"MYO10 is an unstable protein that undergoes ubiquitin-dependent degradation mediated by UbcH7 and β-TrCP1; overexpression of MYO10 increases genomic instability and cGAS/STING-dependent inflammatory signaling, while depletion reduces genomic instability and inflammation.","method":"Protein stability assays, ubiquitination assays; MYO10 overexpression and depletion in cancer cells and mouse tumor models; cGAS/STING pathway readouts","journal":"Science advances","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (ubiquitination assays, in vivo tumor models, inflammatory pathway measurements) in single lab","pmids":["34524844"],"is_preprint":false},{"year":2023,"finding":"MYO10 contains a degron motif with phosphorylation residues that mediate β-TrCP1-dependent degradation; phosphorylated MYO10 transiently accumulates during mitosis, localizing first to the centrosome then to the midbody; depletion of MYO10 or expression of degron mutants disrupts mitosis and increases genomic instability and inflammation.","method":"Degron motif characterization; phosphorylation-site mutagenesis; spatiotemporal localization imaging during mitosis; MYO10 depletion and mutant expression with mitotic phenotype readouts; Taxol sensitivity assays","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — mutagenesis of phosphorylation/degron sites combined with live-cell localization and functional mitotic phenotype readouts, single lab","pmids":["37200188"],"is_preprint":false},{"year":2022,"finding":"MYO10 interacts with and stabilizes RACK1 protein; MYO10 promotes colorectal cancer cell progression and metastasis through ubiquitination-mediated RACK1 degradation and activation of integrin/Src/FAK signaling.","method":"MYO10 knockout in CRC cells; LC-MS/MS identification of RACK1 as MYO10-interacting partner; Co-IP validation; ubiquitination assays; in vitro proliferation/invasion/migration assays; in vivo metastasis model","journal":"Cancer science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP with MS identification plus functional rescue, single lab with in vitro and in vivo validation","pmids":["35912545"],"is_preprint":false},{"year":2022,"finding":"MYO10 promotes filopodia-based formation or maintenance of actin-rich transzonal projections (TZPs) from granulosa cells to oocytes during folliculogenesis; RNAi depletion of MYO10 in mouse granulosa cell-oocyte complexes reduces MYO10 foci by 52% and actin-TZPs by 28%.","method":"RNAi knockdown of MYO10 in mouse granulosa cell-oocyte complexes; immunofluorescence for MYO10 and actin; EGF treatment as positive control for TZP reduction; analysis in both mouse and human follicles","journal":"Biology of reproduction","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with quantitative morphological readout, validated in two species, single lab","pmids":["35470858"],"is_preprint":false},{"year":2022,"finding":"MYO10-filopodia support basement membrane integrity at pre-invasive tumor boundaries; MYO10 depletion in DCIS xenografts leads to compromised basement membranes, poorly defined borders, and increased cancer-cell dispersal, while MYO10 promotes filopodia and cell invasion in vitro.","method":"MYO10 depletion; in vitro invasion assays; DCIS xenograft mouse models; immunofluorescence for basement membrane markers; analysis of EMT markers","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 2 / Moderate — loss-of-function in both in vitro and in vivo xenograft models with multiple orthogonal readouts (BM integrity, invasion, EMT markers)","pmids":["36283390"],"is_preprint":false},{"year":2023,"finding":"The tail domain of Myo10 is crucial for promoting long filopodia; truncation of the tail decreases filopodial formation and length, while mutations in the coiled-coil domain disrupt Myo10 movement toward filopodial tips and filopodial elongation; filopodia elongate through multiple elongation cycles supported by the Myo10 tail.","method":"Overexpression of Myo10 full-length, tail-truncated (Myo10 HMM), and coiled-coil mutant constructs; quantification of filopodial number and length; live-cell imaging of Myo10 tip motility","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain-deletion and point-mutation constructs with quantitative filopodial readouts, single lab","pmids":["38043799"],"is_preprint":false},{"year":2025,"finding":"A mutation in the actin-binding interface of Myo10 (analogous to the 'jordan' mutation in Myo15A) significantly decreases filopodia initiation and Myo10 tip intensity, and reduces intrafilopodial motility velocity by 40%, indicating the major role of Myo10 is to reorganize cortical actin filaments at the membrane-cortex interface during filopodium initiation rather than promoting elongation by reducing membrane tension.","method":"Site-directed mutagenesis of actin-binding interface; quantitative analysis of filopodia number, length, and Myo10 tip enrichment; live-cell imaging of intrafilopodial motility in multiple cell lines","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — mutagenesis with quantitative functional readouts, but preprint and single lab","pmids":["bio_10.1101_2025.05.29.656896"],"is_preprint":true},{"year":2025,"finding":"MYO10 knockdown in HeLa and COS7 cells reduces filopodia at cell edges, impairs cell migration, reduces proliferation, and increases spreading on laminin-coated substrates, suggesting altered integrin activation and cytoskeletal linkage.","method":"Lentiviral shRNA knockdown; wound healing assay; filopodia quantification; cell spreading assay on laminin","journal":"microPublication biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — loss-of-function with multiple readouts but single lab and limited mechanistic depth","pmids":["41050330"],"is_preprint":false}],"current_model":"MYO10 (Myosin X) is an unconventional actin-based motor protein that uses its motor domain to transport itself to filopodial tips via intrafilopodial motility, where it reorganizes cortical actin at the membrane-cortex interface to initiate filopodia; its tail domain (including coiled-coil for dimerization, PH domains for PtdIns(3,4,5)P3 binding, MyTH4, and FERM domains) mediates cargo interactions and is required for filopodial elongation, tunneling nanotube formation, axon development, and basement membrane maintenance; MYO10 protein stability is regulated by β-TrCP1-dependent ubiquitin-mediated degradation through a phosphorylated degron motif, with phosphorylated MYO10 transiently localizing to centrosomes and midbody during mitosis to regulate genome stability and cGAS/STING-dependent inflammatory signaling, while also interacting with RACK1 to activate integrin/Src/FAK signaling in cancer cells."},"narrative":{"mechanistic_narrative":"MYO10 (Myosin X) is an unconventional actin-based motor that drives the initiation and elongation of filopodia and related actin-rich membrane protrusions across neuronal, immune, reproductive, and epithelial contexts [PMID:16371656, PMID:28289096, PMID:35470858]. Its motor domain is required to target the protein to filopodial tips and to power intrafilopodial motility [PMID:16371656], with the actin-binding interface functioning to reorganize cortical actin filaments at the membrane-cortex interface during filopodium initiation [PMID:bio_10.1101_2025.05.29.656896]; the tail domain, including its coiled-coil dimerization region, is in turn required for movement toward tips and for sustained filopodial elongation [PMID:38043799]. Beyond canonical filopodia, MYO10 promotes tunneling nanotube formation through the F2 lobe of its FERM domain [PMID:23886947] and is recruited to PtdIns(3,4,5)P3 via its PH domain to drive axon formation [PMID:22590642]. The brain additionally expresses a headless isoform lacking the motor domain that localizes to the plasma membrane but does not induce filopodia, while full-length motorized MYO10 is required for prenatal development including neural tube closure and digit formation [PMID:16371656, PMID:30679680]. Through its filopodial activity MYO10 supports N-cadherin-mediated neurogenic migration [PMID:25491426], transzonal projections during folliculogenesis [PMID:35470858], and basement-membrane integrity at pre-invasive tumor boundaries, limiting cancer-cell dispersal [PMID:36283390]. MYO10 is an unstable protein degraded via a phosphorylated degron motif by UbcH7 and β-TrCP1; phosphorylated MYO10 transiently accumulates at the centrosome and midbody during mitosis, and its dysregulation increases genomic instability and cGAS/STING-dependent inflammatory signaling [PMID:34524844, PMID:37200188]. In colorectal cancer it additionally interacts with RACK1 and activates integrin/Src/FAK signaling to promote progression and metastasis [PMID:35912545].","teleology":[{"year":2006,"claim":"Established that the MYO10 motor domain is mechanistically necessary for filopodial tip targeting and intrafilopodial motility, and that the brain expresses a distinct headless isoform retaining only the tail modules.","evidence":"Live-cell imaging of GFP-tagged full-length versus headless constructs plus immunoblot/immunofluorescence in CAD neuronal cells and mouse brain","pmids":["16371656"],"confidence":"High","gaps":["Did not define how the motor domain engages cortical actin","Functional role of the headless isoform left unresolved"]},{"year":2012,"claim":"Showed that PH-domain recruitment of MYO10 to PtdIns(3,4,5)P3 drives axon formation, linking phosphoinositide signaling to MYO10-dependent neurite specification independent of motor activity in the gain-of-function setting.","evidence":"RNAi knockdown and EGFP-tagged mutant overexpression in hippocampal neurons with in vivo neocortical migration assay","pmids":["22590642"],"confidence":"High","gaps":["Downstream cargo at the axon tip not identified","Relationship to filopodial initiation machinery unclear"]},{"year":2013,"claim":"Demonstrated that MYO10 promotes tunneling nanotube formation and vesicle transfer, requiring both motor and tail (specifically the FERM F2 lobe) and acting independently of integrin and N-cadherin binding.","evidence":"Domain-deletion/mutation constructs with TNT number and vesicle-transfer quantification in CAD cells","pmids":["23886947"],"confidence":"High","gaps":["F2-lobe binding partner for TNT formation not identified","Mechanistic distinction between TNT and filopodia formation unresolved"]},{"year":2014,"claim":"Connected MYO10 filopodial function to neurogenic migration by showing N-cadherin can rescue the migration deficit of MYO10 loss, implicating cell-matrix adhesion and polarity.","evidence":"shRNA knockdown in NLT cells with wound-healing/Golgi-polarity, adhesion, and N-cadherin rescue assays","pmids":["25491426"],"confidence":"Medium","gaps":["Direct physical link between MYO10 and N-cadherin not established here","Limited mechanistic depth, single lab"]},{"year":2017,"claim":"Placed MYO10 downstream of Cdc42 specifically in filopodia induction, dissociating its role from general cell morphology and phagocytosis.","evidence":"Myo10 knockout mice and live imaging of Lifeact-EGFP macrophages with phagocytosis assays","pmids":["28289096"],"confidence":"High","gaps":["Molecular link between Cdc42 and MYO10 not defined","Physiological consequence of macrophage filopodia loss not assessed"]},{"year":2019,"claim":"Distinguished motorized from headless MYO10 in vivo, showing full-length protein is required for prenatal development and vasculature regression while the headless isoform localizes to membrane without inducing filopodia.","evidence":"Isoform-specific reporter knockout mice with MRI, retinal whole-mounts, and in vitro filopodia assays","pmids":["30679680"],"confidence":"High","gaps":["Mechanism of membrane targeting of headless isoform independent of MyTH4-FERM unexplained","Tissue-specific developmental targets not pinpointed"]},{"year":2021,"claim":"Revealed that MYO10 is an unstable protein controlled by UbcH7/β-TrCP1 ubiquitin-mediated degradation and that its levels gate genomic instability and cGAS/STING inflammatory signaling.","evidence":"Protein stability and ubiquitination assays with overexpression/depletion in cancer cells and mouse tumor models","pmids":["34524844"],"confidence":"High","gaps":["Kinase generating the degron phosphorylation not identified at this stage","Mechanistic link from a motor protein to genome stability unclear"]},{"year":2022,"claim":"Extended MYO10 filopodial function to tissue boundaries and adhesion signaling: it maintains basement-membrane integrity limiting tumor dispersal, supports transzonal projections in folliculogenesis, and stabilizes RACK1 to activate integrin/Src/FAK signaling in colorectal cancer.","evidence":"MYO10 depletion in DCIS xenografts and granulosa-oocyte complexes; LC-MS/MS, Co-IP, ubiquitination and metastasis assays in CRC cells","pmids":["36283390","35470858","35912545"],"confidence":"Medium","gaps":["RACK1 interaction rests on a single lab's Co-IP/MS","How filopodia mechanically preserve basement membrane not resolved"]},{"year":2023,"claim":"Defined a phosphorylated degron motif driving β-TrCP1-dependent turnover and showed phosphorylated MYO10 transiently localizes to centrosome then midbody during mitosis, mechanistically linking its degradation control to mitotic fidelity and inflammation.","evidence":"Degron and phosphosite mutagenesis with mitotic localization imaging, depletion phenotypes, and Taxol sensitivity assays","pmids":["37200188"],"confidence":"High","gaps":["Identity of the responsible kinase not established","Functional role of MYO10 at centrosome/midbody mechanistically undefined"]},{"year":2025,"claim":"Pinpointed the actin-binding interface as the key element for filopodium initiation, arguing MYO10's primary role is to reorganize cortical actin at the membrane-cortex interface rather than to reduce membrane tension during elongation.","evidence":"Site-directed mutagenesis of the actin-binding interface with quantitative filopodia and intrafilopodial motility imaging across cell lines (preprint)","pmids":["bio_10.1101_2025.05.29.656896"],"confidence":"Medium","gaps":["Preprint, single lab","Direct structural basis of cortical actin reorganization not resolved"]},{"year":null,"claim":"How MYO10's filopodial motor activity is integrated with its mitotic, genome-stability, and inflammatory functions, and what upstream kinase phosphorylates its degron, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["Kinase generating the degron phosphorylation unknown","Mechanistic connection between cytoplasmic motor function and centrosome/midbody role undefined","Direct cargo bound by tail domains in most contexts unidentified"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003774","term_label":"cytoskeletal motor activity","supporting_discovery_ids":[0,12,13]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,13]},{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[3]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,6]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,13]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[8]}],"pathway":[{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[3,6]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[8]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[9]}],"complexes":[],"partners":["RACK1","BTRC","N-CADHERIN"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9HD67","full_name":"Unconventional myosin-X","aliases":["Unconventional myosin-10"],"length_aa":2058,"mass_kda":237.3,"function":"Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. MYO10 binds to actin filaments and actin bundles and functions as a plus end-directed motor. Moves with higher velocity and takes larger steps on actin bundles than on single actin filaments (PubMed:27580874). The tail domain binds to membranous compartments containing phosphatidylinositol 3,4,5-trisphosphate or integrins, and mediates cargo transport along actin filaments. Regulates cell shape, cell spreading and cell adhesion. Stimulates the formation and elongation of filopodia. In hippocampal neurons it induces the formation of dendritic filopodia by trafficking the actin-remodeling protein VASP to the tips of filopodia, where it promotes actin elongation. Plays a role in formation of the podosome belt in osteoclasts Functions as a dominant-negative regulator of isoform 1, suppressing its filopodia-inducing and axon outgrowth-promoting activities. In hippocampal neurons, it increases VASP retention in spine heads to induce spine formation and spine head expansion (By similarity)","subcellular_location":"Cytoplasm, cytosol; Cell projection, lamellipodium; Cell projection, ruffle; Cytoplasm, cytoskeleton; Cell projection, filopodium tip; Cytoplasm, cell cortex; Cell projection, filopodium membrane","url":"https://www.uniprot.org/uniprotkb/Q9HD67/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MYO10","classification":"Not Classified","n_dependent_lines":16,"n_total_lines":1208,"dependency_fraction":0.013245033112582781},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/MYO10","total_profiled":1310},"omim":[{"mim_id":"612759","title":"SYNESTHESIA","url":"https://www.omim.org/entry/612759"},{"mim_id":"601481","title":"MYOSIN X; MYO10","url":"https://www.omim.org/entry/601481"},{"mim_id":"601479","title":"MYOSIN IE; MYO1E","url":"https://www.omim.org/entry/601479"},{"mim_id":"300345","title":"MICROPHTHALMIA/COLOBOMA 1; MCOPCB1","url":"https://www.omim.org/entry/300345"},{"mim_id":"114184","title":"CALMODULIN-LIKE 3; CALML3","url":"https://www.omim.org/entry/114184"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Plasma membrane","reliability":"Supported"},{"location":"Cytosol","reliability":"Supported"},{"location":"Nucleoli rim","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MYO10"},"hgnc":{"alias_symbol":["KIAA0799","MyoX"],"prev_symbol":[]},"alphafold":{"accession":"Q9HD67","domains":[{"cath_id":"-","chopping":"10-58","consensus_level":"medium","plddt":86.2557,"start":10,"end":58},{"cath_id":"1.20.120.720","chopping":"193-224_246-426_573-589","consensus_level":"medium","plddt":91.4436,"start":193,"end":589},{"cath_id":"2.30.29.30","chopping":"1176-1212_1357-1377","consensus_level":"medium","plddt":78.3352,"start":1176,"end":1377},{"cath_id":"2.30.29.30","chopping":"1214-1312","consensus_level":"medium","plddt":79.7703,"start":1214,"end":1312},{"cath_id":"-","chopping":"1414-1480","consensus_level":"medium","plddt":85.4212,"start":1414,"end":1480},{"cath_id":"1.25.40.530","chopping":"1506-1694","consensus_level":"high","plddt":85.0853,"start":1506,"end":1694},{"cath_id":"2.30.29.30","chopping":"1956-2050","consensus_level":"medium","plddt":79.8212,"start":1956,"end":2050}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9HD67","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9HD67-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9HD67-F1-predicted_aligned_error_v6.png","plddt_mean":76.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MYO10","jax_strain_url":"https://www.jax.org/strain/search?query=MYO10"},"sequence":{"accession":"Q9HD67","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9HD67.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9HD67/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9HD67"}},"corpus_meta":[{"pmid":"23886947","id":"PMC_23886947","title":"Myo10 is a key regulator of TNT formation in neuronal cells.","date":"2013","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/23886947","citation_count":145,"is_preprint":false},{"pmid":"25749519","id":"PMC_25749519","title":"NF-κB-mediated miR-124 suppresses metastasis of non-small-cell lung cancer by targeting MYO10.","date":"2015","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/25749519","citation_count":72,"is_preprint":false},{"pmid":"16371656","id":"PMC_16371656","title":"Myo10 in brain: developmental regulation, identification of a headless isoform and dynamics in neurons.","date":"2006","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/16371656","citation_count":69,"is_preprint":false},{"pmid":"32008463","id":"PMC_32008463","title":"Circ-calm4 Serves as an miR-337-3p Sponge to Regulate Myo10 (Myosin 10) and Promote Pulmonary Artery Smooth Muscle Proliferation.","date":"2020","source":"Hypertension (Dallas, Tex. : 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SNHG7 enhances chemoresistance in neuroblastoma through cisplatin-induced autophagy by regulating miR-329-3p/MYO10 axis.","date":"2020","source":"European review for medical and pharmacological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/32329857","citation_count":27,"is_preprint":false},{"pmid":"34524844","id":"PMC_34524844","title":"MYO10 drives genomic instability and inflammation in cancer.","date":"2021","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/34524844","citation_count":24,"is_preprint":false},{"pmid":"22590642","id":"PMC_22590642","title":"PtdIns (3,4,5) P3 recruitment of Myo10 is essential for axon development.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22590642","citation_count":20,"is_preprint":false},{"pmid":"29864913","id":"PMC_29864913","title":"miR-129 inhibits tumor growth and potentiates chemosensitivity of neuroblastoma by targeting MYO10.","date":"2018","source":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","url":"https://pubmed.ncbi.nlm.nih.gov/29864913","citation_count":19,"is_preprint":false},{"pmid":"35912545","id":"PMC_35912545","title":"MYO10 contributes to the malignant phenotypes of colorectal cancer via RACK1 by activating integrin/Src/FAK signaling.","date":"2022","source":"Cancer science","url":"https://pubmed.ncbi.nlm.nih.gov/35912545","citation_count":16,"is_preprint":false},{"pmid":"35470858","id":"PMC_35470858","title":"MYO10 promotes transzonal projection-dependent germ line-somatic contact during mammalian folliculogenesis†.","date":"2022","source":"Biology of reproduction","url":"https://pubmed.ncbi.nlm.nih.gov/35470858","citation_count":15,"is_preprint":false},{"pmid":"31598400","id":"PMC_31598400","title":"Protease activated receptor 2 mediates tryptase-induced cell migration through MYO10 in colorectal cancer.","date":"2019","source":"American journal of cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/31598400","citation_count":12,"is_preprint":false},{"pmid":"30679680","id":"PMC_30679680","title":"Phenotypic analysis of Myo10 knockout (Myo10tm2/tm2) mice lacking full-length (motorized) but not brain-specific headless myosin X.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/30679680","citation_count":11,"is_preprint":false},{"pmid":"37200188","id":"PMC_37200188","title":"MYO10 regulates genome stability and cancer inflammation through mediating mitosis.","date":"2023","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/37200188","citation_count":7,"is_preprint":false},{"pmid":"25491426","id":"PMC_25491426","title":"Myo10 is required for neurogenic cell adhesion and migration.","date":"2014","source":"In vitro cellular & developmental biology. Animal","url":"https://pubmed.ncbi.nlm.nih.gov/25491426","citation_count":6,"is_preprint":false},{"pmid":"38043799","id":"PMC_38043799","title":"Myo10 tail is crucial for promoting long filopodia.","date":"2023","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/38043799","citation_count":5,"is_preprint":false},{"pmid":"23742061","id":"PMC_23742061","title":"Cloning, characterization, and promoter analysis of mouse Myo10 gene.","date":"2013","source":"Nucleosides, nucleotides & nucleic acids","url":"https://pubmed.ncbi.nlm.nih.gov/23742061","citation_count":1,"is_preprint":false},{"pmid":"41050330","id":"PMC_41050330","title":"Cells stably expressing shRNA against MYO10 display altered cell motility.","date":"2025","source":"microPublication biology","url":"https://pubmed.ncbi.nlm.nih.gov/41050330","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.05.29.656896","title":"Modulation of Filopodial Myosin Function","date":"2025-05-29","source":"bioRxiv","url":"https://doi.org/10.1101/2025.05.29.656896","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":11378,"output_tokens":3871,"usd":0.0461,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11477,"output_tokens":3678,"usd":0.074667,"stage2_stop_reason":"end_turn"},"total_usd":0.120767,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2006,\n      \"finding\": \"Full-length Myo10 (with motor domain) localizes to filopodial tips and undergoes intrafilopodial motility in neuronal CAD cells, while headless Myo10 (lacking the motor domain) does not localize to filopodial tips and does not undergo intrafilopodial motility, demonstrating the motor domain is necessary for these activities.\",\n      \"method\": \"Live cell imaging of GFP-tagged full-length vs. headless Myo10 constructs in transfected CAD neuronal cells\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct live-cell imaging with domain-deletion constructs in a neuronal model, replicated finding consistent with multiple studies\",\n      \"pmids\": [\"16371656\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Brain expresses a headless isoform of Myo10 that lacks the myosin head (motor) domain but retains three PH domains, a MyTH4 domain, and a FERM domain; both full-length and headless Myo10 are developmentally regulated in mouse brain.\",\n      \"method\": \"Immunoblotting and immunofluorescence of mouse brain tissue and CAD cells; GFP-construct transfection\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (immunoblot, immunofluorescence, functional GFP constructs) in a single focused study\",\n      \"pmids\": [\"16371656\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Myo10 promotes tunneling nanotube (TNT) formation in neuronal CAD cells; both the motor domain and the tail domain are required, with the F2 lobe of the FERM domain within the tail specifically necessary for TNT formation, independent of integrin and N-cadherin binding.\",\n      \"method\": \"Overexpression and domain-deletion/mutation constructs in CAD cells; quantification of TNT number and vesicle transfer\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain-deletion analysis with functional readout (TNT number, vesicle transfer), single lab with multiple constructs\",\n      \"pmids\": [\"23886947\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Recruitment of Myo10 to phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) via its PH domain is essential for axon formation; Myo10 knockdown impairs axon outgrowth, and ectopic expression of Myo10 mutants induces multiple axon-like neurites in a motor-independent manner.\",\n      \"method\": \"RNAi knockdown, EGFP-tagged Myo10 mutant overexpression in hippocampal neurons; immunofluorescence with Tau-1 and Tuj1 markers; in vivo neuronal migration assay in developing neocortex\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function and gain-of-function with domain mutants, both in vitro and in vivo validation\",\n      \"pmids\": [\"22590642\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Myo10 knockout macrophages display markedly reduced filopodia formation but have normal morphology, motility, and phagocytic cup formation, placing Myo10 downstream of Cdc42 specifically in filopodia induction rather than general macrophage morphology or phagocytosis.\",\n      \"method\": \"Myo10 knockout mice; spinning disk confocal live-cell imaging of Lifeact-EGFP macrophages; phagocytosis assays with E. coli and zymosan particles\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic knockout with multiple orthogonal functional readouts (filopodia quantification, phagocytosis assays, live imaging)\",\n      \"pmids\": [\"28289096\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Myo10 knockdown in NLT neuronal cells impairs cell motility, disrupts cell polarity (random orientation of Golgi), and decreases cell-matrix adhesion; N-cadherin expression rescues the migration deficiency caused by Myo10 knockdown, indicating Myo10 promotes neurogenic cell migration through N-cadherin-mediated cell adhesion.\",\n      \"method\": \"shRNA knockdown in NLT cells; wound healing assay with Golgi staining for polarity; cell-matrix adhesion assay; N-cadherin rescue in cell aggregate and collagen gel assays\",\n      \"journal\": \"In vitro cellular & developmental biology. Animal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab, loss-of-function with rescue experiment, but limited mechanistic depth\",\n      \"pmids\": [\"25491426\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Full-length (motorized) Myo10 is required for normal prenatal development (neural tube closure, digit formation) and postnatal hyaloid vasculature regression in mice; the headless Myo10 isoform does not induce filopodia but localizes strongly to the plasma membrane independent of the MyTH4-FERM domain.\",\n      \"method\": \"Myo10tm2 reporter knockout mice lacking full-length but not headless Myo10; MRI of brain, retinal whole-mount preparations; in vitro filopodia assays with headless Myo10\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — isoform-specific knockout mouse with multiple orthogonal phenotypic readouts plus in vitro domain localization studies\",\n      \"pmids\": [\"30679680\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"MYO10 is an unstable protein that undergoes ubiquitin-dependent degradation mediated by UbcH7 and β-TrCP1; overexpression of MYO10 increases genomic instability and cGAS/STING-dependent inflammatory signaling, while depletion reduces genomic instability and inflammation.\",\n      \"method\": \"Protein stability assays, ubiquitination assays; MYO10 overexpression and depletion in cancer cells and mouse tumor models; cGAS/STING pathway readouts\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (ubiquitination assays, in vivo tumor models, inflammatory pathway measurements) in single lab\",\n      \"pmids\": [\"34524844\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"MYO10 contains a degron motif with phosphorylation residues that mediate β-TrCP1-dependent degradation; phosphorylated MYO10 transiently accumulates during mitosis, localizing first to the centrosome then to the midbody; depletion of MYO10 or expression of degron mutants disrupts mitosis and increases genomic instability and inflammation.\",\n      \"method\": \"Degron motif characterization; phosphorylation-site mutagenesis; spatiotemporal localization imaging during mitosis; MYO10 depletion and mutant expression with mitotic phenotype readouts; Taxol sensitivity assays\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — mutagenesis of phosphorylation/degron sites combined with live-cell localization and functional mitotic phenotype readouts, single lab\",\n      \"pmids\": [\"37200188\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"MYO10 interacts with and stabilizes RACK1 protein; MYO10 promotes colorectal cancer cell progression and metastasis through ubiquitination-mediated RACK1 degradation and activation of integrin/Src/FAK signaling.\",\n      \"method\": \"MYO10 knockout in CRC cells; LC-MS/MS identification of RACK1 as MYO10-interacting partner; Co-IP validation; ubiquitination assays; in vitro proliferation/invasion/migration assays; in vivo metastasis model\",\n      \"journal\": \"Cancer science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP with MS identification plus functional rescue, single lab with in vitro and in vivo validation\",\n      \"pmids\": [\"35912545\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"MYO10 promotes filopodia-based formation or maintenance of actin-rich transzonal projections (TZPs) from granulosa cells to oocytes during folliculogenesis; RNAi depletion of MYO10 in mouse granulosa cell-oocyte complexes reduces MYO10 foci by 52% and actin-TZPs by 28%.\",\n      \"method\": \"RNAi knockdown of MYO10 in mouse granulosa cell-oocyte complexes; immunofluorescence for MYO10 and actin; EGF treatment as positive control for TZP reduction; analysis in both mouse and human follicles\",\n      \"journal\": \"Biology of reproduction\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with quantitative morphological readout, validated in two species, single lab\",\n      \"pmids\": [\"35470858\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"MYO10-filopodia support basement membrane integrity at pre-invasive tumor boundaries; MYO10 depletion in DCIS xenografts leads to compromised basement membranes, poorly defined borders, and increased cancer-cell dispersal, while MYO10 promotes filopodia and cell invasion in vitro.\",\n      \"method\": \"MYO10 depletion; in vitro invasion assays; DCIS xenograft mouse models; immunofluorescence for basement membrane markers; analysis of EMT markers\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function in both in vitro and in vivo xenograft models with multiple orthogonal readouts (BM integrity, invasion, EMT markers)\",\n      \"pmids\": [\"36283390\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"The tail domain of Myo10 is crucial for promoting long filopodia; truncation of the tail decreases filopodial formation and length, while mutations in the coiled-coil domain disrupt Myo10 movement toward filopodial tips and filopodial elongation; filopodia elongate through multiple elongation cycles supported by the Myo10 tail.\",\n      \"method\": \"Overexpression of Myo10 full-length, tail-truncated (Myo10 HMM), and coiled-coil mutant constructs; quantification of filopodial number and length; live-cell imaging of Myo10 tip motility\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain-deletion and point-mutation constructs with quantitative filopodial readouts, single lab\",\n      \"pmids\": [\"38043799\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"A mutation in the actin-binding interface of Myo10 (analogous to the 'jordan' mutation in Myo15A) significantly decreases filopodia initiation and Myo10 tip intensity, and reduces intrafilopodial motility velocity by 40%, indicating the major role of Myo10 is to reorganize cortical actin filaments at the membrane-cortex interface during filopodium initiation rather than promoting elongation by reducing membrane tension.\",\n      \"method\": \"Site-directed mutagenesis of actin-binding interface; quantitative analysis of filopodia number, length, and Myo10 tip enrichment; live-cell imaging of intrafilopodial motility in multiple cell lines\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — mutagenesis with quantitative functional readouts, but preprint and single lab\",\n      \"pmids\": [\"bio_10.1101_2025.05.29.656896\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"MYO10 knockdown in HeLa and COS7 cells reduces filopodia at cell edges, impairs cell migration, reduces proliferation, and increases spreading on laminin-coated substrates, suggesting altered integrin activation and cytoskeletal linkage.\",\n      \"method\": \"Lentiviral shRNA knockdown; wound healing assay; filopodia quantification; cell spreading assay on laminin\",\n      \"journal\": \"microPublication biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — loss-of-function with multiple readouts but single lab and limited mechanistic depth\",\n      \"pmids\": [\"41050330\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MYO10 (Myosin X) is an unconventional actin-based motor protein that uses its motor domain to transport itself to filopodial tips via intrafilopodial motility, where it reorganizes cortical actin at the membrane-cortex interface to initiate filopodia; its tail domain (including coiled-coil for dimerization, PH domains for PtdIns(3,4,5)P3 binding, MyTH4, and FERM domains) mediates cargo interactions and is required for filopodial elongation, tunneling nanotube formation, axon development, and basement membrane maintenance; MYO10 protein stability is regulated by β-TrCP1-dependent ubiquitin-mediated degradation through a phosphorylated degron motif, with phosphorylated MYO10 transiently localizing to centrosomes and midbody during mitosis to regulate genome stability and cGAS/STING-dependent inflammatory signaling, while also interacting with RACK1 to activate integrin/Src/FAK signaling in cancer cells.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MYO10 (Myosin X) is an unconventional actin-based motor that drives the initiation and elongation of filopodia and related actin-rich membrane protrusions across neuronal, immune, reproductive, and epithelial contexts [#0, #4, #10]. Its motor domain is required to target the protein to filopodial tips and to power intrafilopodial motility [#0], with the actin-binding interface functioning to reorganize cortical actin filaments at the membrane-cortex interface during filopodium initiation [#13]; the tail domain, including its coiled-coil dimerization region, is in turn required for movement toward tips and for sustained filopodial elongation [#12]. Beyond canonical filopodia, MYO10 promotes tunneling nanotube formation through the F2 lobe of its FERM domain [#2] and is recruited to PtdIns(3,4,5)P3 via its PH domain to drive axon formation [#3]. The brain additionally expresses a headless isoform lacking the motor domain that localizes to the plasma membrane but does not induce filopodia, while full-length motorized MYO10 is required for prenatal development including neural tube closure and digit formation [#1, #6]. Through its filopodial activity MYO10 supports N-cadherin-mediated neurogenic migration [#5], transzonal projections during folliculogenesis [#10], and basement-membrane integrity at pre-invasive tumor boundaries, limiting cancer-cell dispersal [#11]. MYO10 is an unstable protein degraded via a phosphorylated degron motif by UbcH7 and \\u03b2-TrCP1; phosphorylated MYO10 transiently accumulates at the centrosome and midbody during mitosis, and its dysregulation increases genomic instability and cGAS/STING-dependent inflammatory signaling [#7, #8]. In colorectal cancer it additionally interacts with RACK1 and activates integrin/Src/FAK signaling to promote progression and metastasis [#9].\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Established that the MYO10 motor domain is mechanistically necessary for filopodial tip targeting and intrafilopodial motility, and that the brain expresses a distinct headless isoform retaining only the tail modules.\",\n      \"evidence\": \"Live-cell imaging of GFP-tagged full-length versus headless constructs plus immunoblot/immunofluorescence in CAD neuronal cells and mouse brain\",\n      \"pmids\": [\"16371656\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define how the motor domain engages cortical actin\", \"Functional role of the headless isoform left unresolved\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Showed that PH-domain recruitment of MYO10 to PtdIns(3,4,5)P3 drives axon formation, linking phosphoinositide signaling to MYO10-dependent neurite specification independent of motor activity in the gain-of-function setting.\",\n      \"evidence\": \"RNAi knockdown and EGFP-tagged mutant overexpression in hippocampal neurons with in vivo neocortical migration assay\",\n      \"pmids\": [\"22590642\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Downstream cargo at the axon tip not identified\", \"Relationship to filopodial initiation machinery unclear\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Demonstrated that MYO10 promotes tunneling nanotube formation and vesicle transfer, requiring both motor and tail (specifically the FERM F2 lobe) and acting independently of integrin and N-cadherin binding.\",\n      \"evidence\": \"Domain-deletion/mutation constructs with TNT number and vesicle-transfer quantification in CAD cells\",\n      \"pmids\": [\"23886947\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"F2-lobe binding partner for TNT formation not identified\", \"Mechanistic distinction between TNT and filopodia formation unresolved\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Connected MYO10 filopodial function to neurogenic migration by showing N-cadherin can rescue the migration deficit of MYO10 loss, implicating cell-matrix adhesion and polarity.\",\n      \"evidence\": \"shRNA knockdown in NLT cells with wound-healing/Golgi-polarity, adhesion, and N-cadherin rescue assays\",\n      \"pmids\": [\"25491426\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct physical link between MYO10 and N-cadherin not established here\", \"Limited mechanistic depth, single lab\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Placed MYO10 downstream of Cdc42 specifically in filopodia induction, dissociating its role from general cell morphology and phagocytosis.\",\n      \"evidence\": \"Myo10 knockout mice and live imaging of Lifeact-EGFP macrophages with phagocytosis assays\",\n      \"pmids\": [\"28289096\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular link between Cdc42 and MYO10 not defined\", \"Physiological consequence of macrophage filopodia loss not assessed\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Distinguished motorized from headless MYO10 in vivo, showing full-length protein is required for prenatal development and vasculature regression while the headless isoform localizes to membrane without inducing filopodia.\",\n      \"evidence\": \"Isoform-specific reporter knockout mice with MRI, retinal whole-mounts, and in vitro filopodia assays\",\n      \"pmids\": [\"30679680\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of membrane targeting of headless isoform independent of MyTH4-FERM unexplained\", \"Tissue-specific developmental targets not pinpointed\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Revealed that MYO10 is an unstable protein controlled by UbcH7/\\u03b2-TrCP1 ubiquitin-mediated degradation and that its levels gate genomic instability and cGAS/STING inflammatory signaling.\",\n      \"evidence\": \"Protein stability and ubiquitination assays with overexpression/depletion in cancer cells and mouse tumor models\",\n      \"pmids\": [\"34524844\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinase generating the degron phosphorylation not identified at this stage\", \"Mechanistic link from a motor protein to genome stability unclear\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Extended MYO10 filopodial function to tissue boundaries and adhesion signaling: it maintains basement-membrane integrity limiting tumor dispersal, supports transzonal projections in folliculogenesis, and stabilizes RACK1 to activate integrin/Src/FAK signaling in colorectal cancer.\",\n      \"evidence\": \"MYO10 depletion in DCIS xenografts and granulosa-oocyte complexes; LC-MS/MS, Co-IP, ubiquitination and metastasis assays in CRC cells\",\n      \"pmids\": [\"36283390\", \"35470858\", \"35912545\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"RACK1 interaction rests on a single lab's Co-IP/MS\", \"How filopodia mechanically preserve basement membrane not resolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined a phosphorylated degron motif driving \\u03b2-TrCP1-dependent turnover and showed phosphorylated MYO10 transiently localizes to centrosome then midbody during mitosis, mechanistically linking its degradation control to mitotic fidelity and inflammation.\",\n      \"evidence\": \"Degron and phosphosite mutagenesis with mitotic localization imaging, depletion phenotypes, and Taxol sensitivity assays\",\n      \"pmids\": [\"37200188\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Identity of the responsible kinase not established\", \"Functional role of MYO10 at centrosome/midbody mechanistically undefined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Pinpointed the actin-binding interface as the key element for filopodium initiation, arguing MYO10's primary role is to reorganize cortical actin at the membrane-cortex interface rather than to reduce membrane tension during elongation.\",\n      \"evidence\": \"Site-directed mutagenesis of the actin-binding interface with quantitative filopodia and intrafilopodial motility imaging across cell lines (preprint)\",\n      \"pmids\": [\"bio_10.1101_2025.05.29.656896\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Preprint, single lab\", \"Direct structural basis of cortical actin reorganization not resolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How MYO10's filopodial motor activity is integrated with its mitotic, genome-stability, and inflammatory functions, and what upstream kinase phosphorylates its degron, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Kinase generating the degron phosphorylation unknown\", \"Mechanistic connection between cytoplasmic motor function and centrosome/midbody role undefined\", \"Direct cargo bound by tail domains in most contexts unidentified\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003774\", \"supporting_discovery_ids\": [0, 12, 13]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 13]},\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 6]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 13]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [8]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [3, 6]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [8]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [9]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"RACK1\", \"BTRC\", \"N-cadherin\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}