{"gene":"MYO10","run_date":"2026-04-29T11:37:56","timeline":{"discoveries":[{"year":2006,"finding":"Full-length Myo10 localizes to filopodial tips and undergoes intrafilopodial motility, requiring the motor domain; headless Myo10 (lacking the motor domain) fails to localize to filopodial tips or 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 neuronal CAD cells","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 — direct live-cell imaging with domain-deletion constructs, replicated across isoforms","pmids":["16371656"],"is_preprint":false},{"year":2006,"finding":"Headless Myo10, a brain-specific isoform lacking the motor domain, is expressed in brain and contains PH, MyTH4, and FERM domains; it localizes to the plasma membrane independently of the MyTH4-FERM domain, unlike full-length Myo10.","method":"Immunoblotting, immunofluorescence, GFP-construct localization in CAD cells and mouse brain","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 — multiple methods but single lab characterization","pmids":["16371656","30679680"],"is_preprint":false},{"year":2012,"finding":"Myo10 is recruited to the plasma membrane via its PH domains binding PtdIns(3,4,5)P3, and this recruitment is essential for axon formation in hippocampal neurons; knockdown of Myo10 impairs axon outgrowth, and ectopic expression of Myo10 with mutated PH domains fails to rescue axon formation.","method":"Immunofluorescence, shRNA knockdown, GFP-tagged Myo10 PH-domain mutant expression in hippocampal neurons, in vivo neocortex radial migration assay","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 — loss-of-function, domain mutants, and in vivo rescue with defined phenotype","pmids":["22590642"],"is_preprint":false},{"year":2013,"finding":"Myo10 promotes TNT (tunneling nanotube) formation in neuronal cells; both the motor and tail domains are required, and specifically the F2 lobe of the FERM domain within the Myo10 tail is necessary for TNT formation, independent of integrin or N-cadherin binding.","method":"Myo10 overexpression/domain-deletion constructs, vesicle transfer assays in co-cultured CAD cells","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 — domain dissection with multiple constructs and functional readout (vesicle transfer)","pmids":["23886947"],"is_preprint":false},{"year":2014,"finding":"Myo10 is required for neurogenic cell migration and cell-matrix adhesion; knockdown of Myo10 impairs cell polarity, directional migration, and adhesion, and N-cadherin rescues migration defects caused by Myo10 knockdown.","method":"shRNA knockdown, wound healing assay, Golgi polarity staining, cell adhesion assay, N-cadherin rescue in NLT cells","journal":"In vitro cellular & developmental biology. Animal","confidence":"Medium","confidence_rationale":"Tier 2 — loss-of-function with rescue, multiple cellular phenotype readouts, single lab","pmids":["25491426"],"is_preprint":false},{"year":2017,"finding":"Myo10 is required for filopodia formation in macrophages; Myo10 knockout macrophages display markedly reduced filopodia but have normal morphology, motility, and phagocytic cup formation, placing Myo10 downstream of Cdc42 in the filopodia-induction pathway.","method":"Myeloid-restricted Cdc42 and Myo10 knockout mice, spinning disk confocal live imaging, phagocytosis assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — genetic KO with epistasis, live imaging, and multiple functional readouts","pmids":["28289096"],"is_preprint":false},{"year":2019,"finding":"Full-length motorized Myo10 is required in vivo for neural tube closure, digit formation, and postnatal hyaloid vasculature regression; mice lacking full-length Myo10 (but retaining headless isoform) develop syndactyly, white belly spots, and exencephaly.","method":"Myo10 reporter knockout mice (Myo10tm2), MRI, retinal whole-mount preparations, histology","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 2 — genetic KO with multiple defined in vivo phenotypic readouts","pmids":["30679680"],"is_preprint":false},{"year":2021,"finding":"MYO10 undergoes ubiquitin-proteasome degradation mediated by UbcH7 (ubiquitin-conjugating enzyme H7) and β-TrCP1 (β-transducin repeat containing protein 1); overexpression of MYO10 increases genomic instability and activates cGAS/STING-dependent inflammatory signaling, while MYO10 depletion reduces genomic instability and inflammation.","method":"Co-immunoprecipitation, ubiquitination assays, MYO10 overexpression/depletion in cancer cell lines and mouse tumor models, cGAS/STING pathway readouts","journal":"Science advances","confidence":"High","confidence_rationale":"Tier 2 — biochemical degradation mechanism plus in vitro and in vivo functional validation with multiple orthogonal methods","pmids":["34524844"],"is_preprint":false},{"year":2022,"finding":"MYO10 interacts with and stabilizes RACK1 protein; MYO10 promotes colorectal cancer cell progression and metastasis by preventing ubiquitination-mediated RACK1 degradation, thereby activating integrin/Src/FAK signaling.","method":"LC-MS/MS proteomics, co-immunoprecipitation, MYO10 knockout in CRC cells, Western blot for RACK1 ubiquitination, in vitro and in vivo metastasis assays","journal":"Cancer science","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP, MS identification of interactor, KO with defined pathway readout","pmids":["35912545"],"is_preprint":false},{"year":2022,"finding":"MYO10 filopodia are required for maintaining a near-continuous extracellular matrix/basement membrane boundary around cancer spheroids; MYO10 depletion in DCIS xenografts leads to compromised basement membranes and increased cancer cell dispersal, whereas MYO10 promotes invasive dissemination at later stages.","method":"MYO10 depletion by RNAi, human DCIS xenografts in mice, 3D spheroid culture, immunofluorescence for BM markers, live imaging","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 2 — in vitro and in vivo loss-of-function with multiple orthogonal structural and functional readouts","pmids":["36283390"],"is_preprint":false},{"year":2022,"finding":"MYO10 promotes formation and maintenance of actin-rich transzonal projections (TZPs) in ovarian follicles; MYO10 protein localizes to foci at the oocyte-granulosa cell interface, and RNAi-mediated depletion reduces MYO10 foci and actin-TZP numbers.","method":"Immunofluorescence localization in mouse and human follicles, RNAi depletion in granulosa cell-oocyte complexes, quantitative TZP analysis","journal":"Biology of reproduction","confidence":"Medium","confidence_rationale":"Tier 2 — loss-of-function with defined cellular phenotype and localization, single lab","pmids":["35470858"],"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 the midbody; depletion of MYO10 or expression of degron mutants disrupts mitosis and increases genomic instability.","method":"Degron mutagenesis, phosphorylation site mapping, cell fractionation, live imaging of MYO10-GFP during mitosis, flow cytometry, genomic instability assays","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 1–2 — mutagenesis of degron/phosphorylation sites combined with live imaging and functional mitosis readouts","pmids":["37200188"],"is_preprint":false},{"year":2023,"finding":"The tail domain of Myo10, including its coiled-coil domain, is essential for promoting long filopodia; truncation of the tail reduces filopodial number and length, while mutations disrupting the coiled-coil domain impair Myo10 tip-directed motility and filopodial elongation through multiple elongation cycles.","method":"GFP-tagged Myo10 tail-truncation and coiled-coil mutant constructs, filopodia length/number quantification, live cell imaging","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 — structure-function mutagenesis with quantitative filopodia assays and live imaging","pmids":["38043799"],"is_preprint":false},{"year":2025,"finding":"A mutation in the conserved actin-binding interface of Myo10 (analogous to the jordan mutation) reduces filopodia initiation and Myo10 tip enrichment, and decreases intrafilopodial motility velocity by ~40%, indicating that Myo10's primary role is to reorganize cortical actin at the membrane-cortex interface during filopodia initiation rather than promoting elongation by reducing membrane tension.","method":"Site-directed mutagenesis of actin-binding interface, quantitative filopodia assays (number, length, tip intensity), live imaging of Myo10-jd in multiple cell lines","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 1 — mutagenesis with quantitative functional readout, but preprint not yet peer-reviewed","pmids":["bio_10.1101_2025.05.29.656896"],"is_preprint":true},{"year":2025,"finding":"MYO10 knockdown in HeLa and COS7 cells reduces filopodia formation, impairs cell migration in wound assays, reduces proliferation, and increases cell spreading on laminin-coated substrates, indicating altered integrin activation and cytoskeletal linkage.","method":"Lentiviral shRNA knockdown, wound healing assay, filopodia quantification, laminin adhesion spreading assay","journal":"microPublication biology","confidence":"Medium","confidence_rationale":"Tier 2 — loss-of-function in two cell lines with multiple phenotypic readouts, single lab","pmids":["41050330"],"is_preprint":false}],"current_model":"MYO10 is an actin-based unconventional myosin that localizes to filopodial tips via its motor domain and is recruited to the plasma membrane through PH domain binding to PtdIns(3,4,5)P3; its tail domain (including coiled-coil and FERM subdomains) supports filopodial elongation and tunneling nanotube formation, while during mitosis it undergoes β-TrCP1/UbcH7-dependent proteasomal degradation regulated by a degron phosphorylation motif, transiently accumulates at centrosomes and midbodies to ensure genomic stability, and in interphase mediates cell migration, adhesion, basement membrane integrity, and cancer metastasis partly through stabilizing RACK1 to activate integrin/Src/FAK signaling."},"narrative":{"teleology":[{"year":2006,"claim":"Establishing that the motor domain is the determinant for filopodial tip localization resolved how MYO10 reaches its site of action—by active transport along actin, not passive diffusion—and revealed a brain-specific headless isoform with distinct membrane-targeting properties.","evidence":"Live-cell GFP imaging of full-length vs. headless Myo10 constructs in CAD neuronal cells","pmids":["16371656"],"confidence":"High","gaps":["Cargo identity carried by MYO10 to filopodial tips unknown","Regulation of headless isoform expression and function uncharacterized","Structural basis of motor domain processivity on actin bundles not defined"]},{"year":2012,"claim":"Demonstrating that PH domain–PtdIns(3,4,5)P3 interaction recruits MYO10 to the plasma membrane and is required for axon outgrowth linked lipid signaling to MYO10 activation and established its role in neuronal polarization.","evidence":"shRNA knockdown, PH-domain mutant rescue, and in vivo neocortex radial migration assay in hippocampal neurons","pmids":["22590642"],"confidence":"High","gaps":["Whether PI3K isoform specificity governs MYO10 recruitment not tested","Downstream effectors mediating axon specification after MYO10 activation unidentified"]},{"year":2013,"claim":"Showing that MYO10 drives tunneling nanotube formation through the F2 lobe of its FERM domain—independent of integrin or cadherin binding—expanded MYO10 function beyond filopodia to intercellular communication conduits.","evidence":"Domain-deletion constructs and vesicle transfer assays in co-cultured CAD cells","pmids":["23886947"],"confidence":"High","gaps":["FERM F2 lobe binding partner that mediates TNT formation not identified","Whether TNT phenotype is relevant in vivo not tested"]},{"year":2017,"claim":"Genetic epistasis in macrophages placed MYO10 downstream of Cdc42 for filopodia induction while showing that phagocytic cup formation and motility are MYO10-independent, delineating the boundaries of MYO10 function in innate immune cells.","evidence":"Myeloid-specific Cdc42 and Myo10 knockout mice, live confocal imaging, phagocytosis assays","pmids":["28289096"],"confidence":"High","gaps":["Signal between Cdc42 activation and MYO10 engagement not identified","Whether filopodia loss affects pathogen sensing in vivo not assessed"]},{"year":2019,"claim":"Full-length MYO10 knockout mice revealed essential in vivo roles in neural tube closure, digit separation, and vascular regression, connecting filopodial function to major developmental morphogenesis programs.","evidence":"Myo10tm2 reporter knockout mice with MRI, retinal whole mounts, and histology","pmids":["30679680"],"confidence":"High","gaps":["Cell-type-specific contributions to neural tube closure not dissected","Whether headless isoform partially compensates in vivo not quantified"]},{"year":2021,"claim":"Identifying β-TrCP1 and UbcH7 as the E3/E2 pair mediating MYO10 proteasomal degradation, and linking MYO10 overexpression to genomic instability and cGAS/STING inflammatory signaling, established MYO10 as a regulated oncoprotein whose levels must be controlled for genome integrity.","evidence":"Co-IP, ubiquitination assays, MYO10 overexpression/depletion in cancer lines and mouse tumor models","pmids":["34524844"],"confidence":"High","gaps":["Kinase responsible for degron phosphorylation not identified at this stage","How MYO10 overexpression mechanistically causes micronuclei formation unclear"]},{"year":2022,"claim":"Three independent studies in 2022 broadened MYO10's functional scope: stabilization of RACK1 to activate integrin/Src/FAK signaling in colorectal cancer metastasis, maintenance of basement membrane integrity around cancer spheroids, and promotion of transzonal projections in ovarian follicles.","evidence":"LC-MS/MS with reciprocal Co-IP and MYO10 KO in CRC cells; RNAi in DCIS xenografts with BM marker imaging; RNAi in granulosa-oocyte complexes with TZP quantification","pmids":["35912545","36283390","35470858"],"confidence":"High","gaps":["How MYO10 prevents RACK1 ubiquitination mechanistically is unknown","Whether BM maintenance and invasive functions of MYO10 are context-dependent or cell-intrinsic not resolved","Molecular basis of TZP formation by MYO10 in follicles not characterized"]},{"year":2023,"claim":"Mapping the phospho-degron that controls β-TrCP1-mediated MYO10 turnover during mitosis, and showing MYO10 transient accumulation at centrosomes and midbodies, established a cell-cycle-regulated role for MYO10 in faithful chromosome segregation distinct from its interphase filopodial function.","evidence":"Degron mutagenesis, phosphorylation site mapping, live MYO10-GFP imaging during mitosis, genomic instability assays","pmids":["37200188"],"confidence":"High","gaps":["Mitotic kinase phosphorylating the degron not conclusively identified","Centrosomal and midbody binding partners of MYO10 during mitosis unknown","Whether mitotic MYO10 function is motor-dependent not tested"]},{"year":2023,"claim":"Demonstrating that the coiled-coil domain is required for sustained tip-directed motility and multiple elongation cycles refined the model from simple tip transport to a processive mechanism involving dimerization-dependent processivity.","evidence":"Coiled-coil mutant and tail-truncation constructs with quantitative filopodia length/number analysis and live imaging","pmids":["38043799"],"confidence":"High","gaps":["Whether coiled-coil mediates dimerization or scaffolding not structurally resolved","Cargo carried during elongation cycles not identified"]},{"year":null,"claim":"Key unresolved questions include the identity of the mitotic kinase phosphorylating the MYO10 degron, the structural basis for MYO10 processivity on bundled actin, whether MYO10's primary role is cortical actin reorganization during filopodia initiation versus membrane tension reduction during elongation, and the molecular mechanism by which MYO10 stabilizes RACK1.","evidence":"","pmids":[],"confidence":"Medium","gaps":["Mitotic kinase identity unknown","Cryo-EM or high-resolution structure of MYO10 on actin bundles lacking","Initiation vs. elongation role debated but not conclusively separated"]}],"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":[0,5,12,13]},{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[2]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[1,2]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,5,12]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[11]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,8]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[6]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[7,11]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[7,11]}],"complexes":[],"partners":["BTRC","UBE2L3","GNB2L1","CDC42"],"other_free_text":[]},"mechanistic_narrative":"MYO10 is an unconventional myosin that drives filopodia formation, cell migration, and intercellular communication by transporting along actin filaments to filopodial tips and reorganizing cortical actin at the membrane–cortex interface. Its motor domain is required for tip-directed intrafilopodial motility, while PH domains recruit it to the plasma membrane via PtdIns(3,4,5)P3 binding, and its tail domain—including coiled-coil and FERM subdomains—supports filopodial elongation, tunneling nanotube formation, and transzonal projection maintenance [PMID:16371656, PMID:22590642, PMID:23886947, PMID:38043799, PMID:35470858]. During mitosis, MYO10 undergoes β-TrCP1/UbcH7-dependent proteasomal degradation controlled by a phosphorylation-sensitive degron; transient accumulation at centrosomes and midbodies is required for accurate chromosome segregation, and its overexpression promotes genomic instability and cGAS/STING inflammatory signaling [PMID:34524844, PMID:37200188]. In vivo, full-length MYO10 is essential for neural tube closure, digit separation, and basement membrane integrity around epithelial structures, and it promotes cancer metastasis in part by stabilizing RACK1 to activate integrin/Src/FAK signaling [PMID:30679680, PMID:36283390, PMID:35912545]."},"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":143,"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. : 1979)","url":"https://pubmed.ncbi.nlm.nih.gov/32008463","citation_count":62,"is_preprint":false},{"pmid":"28289096","id":"PMC_28289096","title":"Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion.","date":"2017","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/28289096","citation_count":47,"is_preprint":false},{"pmid":"26573744","id":"PMC_26573744","title":"MiR-340 suppresses cell migration and invasion by targeting MYO10 in breast cancer.","date":"2015","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/26573744","citation_count":42,"is_preprint":false},{"pmid":"32329857","id":"PMC_32329857","title":"LncRNA 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":"36283390","id":"PMC_36283390","title":"MYO10-filopodia support basement membranes at pre-invasive tumor boundaries.","date":"2022","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/36283390","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":23,"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":14,"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":6,"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":3,"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":10609,"output_tokens":3491,"usd":0.042096},"stage2":{"model":"claude-opus-4-6","input_tokens":6910,"output_tokens":2816,"usd":0.157425},"total_usd":0.199521,"stage1_batch_id":"msgbatch_012ZiiCUBfB62NCTQd4Bk1Jo","stage2_batch_id":"msgbatch_01Xuqq9aUHoQouS7UVGZNStZ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2006,\n      \"finding\": \"Full-length Myo10 localizes to filopodial tips and undergoes intrafilopodial motility, requiring the motor domain; headless Myo10 (lacking the motor domain) fails to localize to filopodial tips or 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 neuronal CAD cells\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct live-cell imaging with domain-deletion constructs, replicated across isoforms\",\n      \"pmids\": [\"16371656\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Headless Myo10, a brain-specific isoform lacking the motor domain, is expressed in brain and contains PH, MyTH4, and FERM domains; it localizes to the plasma membrane independently of the MyTH4-FERM domain, unlike full-length Myo10.\",\n      \"method\": \"Immunoblotting, immunofluorescence, GFP-construct localization in CAD cells and mouse brain\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple methods but single lab characterization\",\n      \"pmids\": [\"16371656\", \"30679680\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Myo10 is recruited to the plasma membrane via its PH domains binding PtdIns(3,4,5)P3, and this recruitment is essential for axon formation in hippocampal neurons; knockdown of Myo10 impairs axon outgrowth, and ectopic expression of Myo10 with mutated PH domains fails to rescue axon formation.\",\n      \"method\": \"Immunofluorescence, shRNA knockdown, GFP-tagged Myo10 PH-domain mutant expression in hippocampal neurons, in vivo neocortex radial migration assay\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function, domain mutants, and in vivo rescue with defined phenotype\",\n      \"pmids\": [\"22590642\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Myo10 promotes TNT (tunneling nanotube) formation in neuronal cells; both the motor and tail domains are required, and specifically the F2 lobe of the FERM domain within the Myo10 tail is necessary for TNT formation, independent of integrin or N-cadherin binding.\",\n      \"method\": \"Myo10 overexpression/domain-deletion constructs, vesicle transfer assays in co-cultured CAD cells\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — domain dissection with multiple constructs and functional readout (vesicle transfer)\",\n      \"pmids\": [\"23886947\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Myo10 is required for neurogenic cell migration and cell-matrix adhesion; knockdown of Myo10 impairs cell polarity, directional migration, and adhesion, and N-cadherin rescues migration defects caused by Myo10 knockdown.\",\n      \"method\": \"shRNA knockdown, wound healing assay, Golgi polarity staining, cell adhesion assay, N-cadherin rescue in NLT cells\",\n      \"journal\": \"In vitro cellular & developmental biology. Animal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function with rescue, multiple cellular phenotype readouts, single lab\",\n      \"pmids\": [\"25491426\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Myo10 is required for filopodia formation in macrophages; Myo10 knockout macrophages display markedly reduced filopodia but have normal morphology, motility, and phagocytic cup formation, placing Myo10 downstream of Cdc42 in the filopodia-induction pathway.\",\n      \"method\": \"Myeloid-restricted Cdc42 and Myo10 knockout mice, spinning disk confocal live imaging, phagocytosis assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic KO with epistasis, live imaging, and multiple functional readouts\",\n      \"pmids\": [\"28289096\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Full-length motorized Myo10 is required in vivo for neural tube closure, digit formation, and postnatal hyaloid vasculature regression; mice lacking full-length Myo10 (but retaining headless isoform) develop syndactyly, white belly spots, and exencephaly.\",\n      \"method\": \"Myo10 reporter knockout mice (Myo10tm2), MRI, retinal whole-mount preparations, histology\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic KO with multiple defined in vivo phenotypic readouts\",\n      \"pmids\": [\"30679680\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"MYO10 undergoes ubiquitin-proteasome degradation mediated by UbcH7 (ubiquitin-conjugating enzyme H7) and β-TrCP1 (β-transducin repeat containing protein 1); overexpression of MYO10 increases genomic instability and activates cGAS/STING-dependent inflammatory signaling, while MYO10 depletion reduces genomic instability and inflammation.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assays, MYO10 overexpression/depletion in cancer cell lines and mouse tumor models, cGAS/STING pathway readouts\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — biochemical degradation mechanism plus in vitro and in vivo functional validation with multiple orthogonal methods\",\n      \"pmids\": [\"34524844\"],\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 by preventing ubiquitination-mediated RACK1 degradation, thereby activating integrin/Src/FAK signaling.\",\n      \"method\": \"LC-MS/MS proteomics, co-immunoprecipitation, MYO10 knockout in CRC cells, Western blot for RACK1 ubiquitination, in vitro and in vivo metastasis assays\",\n      \"journal\": \"Cancer science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP, MS identification of interactor, KO with defined pathway readout\",\n      \"pmids\": [\"35912545\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"MYO10 filopodia are required for maintaining a near-continuous extracellular matrix/basement membrane boundary around cancer spheroids; MYO10 depletion in DCIS xenografts leads to compromised basement membranes and increased cancer cell dispersal, whereas MYO10 promotes invasive dissemination at later stages.\",\n      \"method\": \"MYO10 depletion by RNAi, human DCIS xenografts in mice, 3D spheroid culture, immunofluorescence for BM markers, live imaging\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — in vitro and in vivo loss-of-function with multiple orthogonal structural and functional readouts\",\n      \"pmids\": [\"36283390\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"MYO10 promotes formation and maintenance of actin-rich transzonal projections (TZPs) in ovarian follicles; MYO10 protein localizes to foci at the oocyte-granulosa cell interface, and RNAi-mediated depletion reduces MYO10 foci and actin-TZP numbers.\",\n      \"method\": \"Immunofluorescence localization in mouse and human follicles, RNAi depletion in granulosa cell-oocyte complexes, quantitative TZP analysis\",\n      \"journal\": \"Biology of reproduction\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function with defined cellular phenotype and localization, single lab\",\n      \"pmids\": [\"35470858\"],\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 the midbody; depletion of MYO10 or expression of degron mutants disrupts mitosis and increases genomic instability.\",\n      \"method\": \"Degron mutagenesis, phosphorylation site mapping, cell fractionation, live imaging of MYO10-GFP during mitosis, flow cytometry, genomic instability assays\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — mutagenesis of degron/phosphorylation sites combined with live imaging and functional mitosis readouts\",\n      \"pmids\": [\"37200188\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"The tail domain of Myo10, including its coiled-coil domain, is essential for promoting long filopodia; truncation of the tail reduces filopodial number and length, while mutations disrupting the coiled-coil domain impair Myo10 tip-directed motility and filopodial elongation through multiple elongation cycles.\",\n      \"method\": \"GFP-tagged Myo10 tail-truncation and coiled-coil mutant constructs, filopodia length/number quantification, live cell imaging\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — structure-function mutagenesis with quantitative filopodia assays and live imaging\",\n      \"pmids\": [\"38043799\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"A mutation in the conserved actin-binding interface of Myo10 (analogous to the jordan mutation) reduces filopodia initiation and Myo10 tip enrichment, and decreases intrafilopodial motility velocity by ~40%, indicating that Myo10's primary role is to reorganize cortical actin at the membrane-cortex interface during filopodia initiation rather than promoting elongation by reducing membrane tension.\",\n      \"method\": \"Site-directed mutagenesis of actin-binding interface, quantitative filopodia assays (number, length, tip intensity), live imaging of Myo10-jd in multiple cell lines\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — mutagenesis with quantitative functional readout, but preprint not yet peer-reviewed\",\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 formation, impairs cell migration in wound assays, reduces proliferation, and increases cell spreading on laminin-coated substrates, indicating altered integrin activation and cytoskeletal linkage.\",\n      \"method\": \"Lentiviral shRNA knockdown, wound healing assay, filopodia quantification, laminin adhesion spreading assay\",\n      \"journal\": \"microPublication biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function in two cell lines with multiple phenotypic readouts, single lab\",\n      \"pmids\": [\"41050330\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MYO10 is an actin-based unconventional myosin that localizes to filopodial tips via its motor domain and is recruited to the plasma membrane through PH domain binding to PtdIns(3,4,5)P3; its tail domain (including coiled-coil and FERM subdomains) supports filopodial elongation and tunneling nanotube formation, while during mitosis it undergoes β-TrCP1/UbcH7-dependent proteasomal degradation regulated by a degron phosphorylation motif, transiently accumulates at centrosomes and midbodies to ensure genomic stability, and in interphase mediates cell migration, adhesion, basement membrane integrity, and cancer metastasis partly through stabilizing RACK1 to activate integrin/Src/FAK signaling.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"MYO10 is an unconventional myosin that drives filopodia formation, cell migration, and intercellular communication by transporting along actin filaments to filopodial tips and reorganizing cortical actin at the membrane–cortex interface. Its motor domain is required for tip-directed intrafilopodial motility, while PH domains recruit it to the plasma membrane via PtdIns(3,4,5)P3 binding, and its tail domain—including coiled-coil and FERM subdomains—supports filopodial elongation, tunneling nanotube formation, and transzonal projection maintenance [PMID:16371656, PMID:22590642, PMID:23886947, PMID:38043799, PMID:35470858]. During mitosis, MYO10 undergoes β-TrCP1/UbcH7-dependent proteasomal degradation controlled by a phosphorylation-sensitive degron; transient accumulation at centrosomes and midbodies is required for accurate chromosome segregation, and its overexpression promotes genomic instability and cGAS/STING inflammatory signaling [PMID:34524844, PMID:37200188]. In vivo, full-length MYO10 is essential for neural tube closure, digit separation, and basement membrane integrity around epithelial structures, and it promotes cancer metastasis in part by stabilizing RACK1 to activate integrin/Src/FAK signaling [PMID:30679680, PMID:36283390, PMID:35912545].\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Establishing that the motor domain is the determinant for filopodial tip localization resolved how MYO10 reaches its site of action—by active transport along actin, not passive diffusion—and revealed a brain-specific headless isoform with distinct membrane-targeting properties.\",\n      \"evidence\": \"Live-cell GFP imaging of full-length vs. headless Myo10 constructs in CAD neuronal cells\",\n      \"pmids\": [\"16371656\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Cargo identity carried by MYO10 to filopodial tips unknown\",\n        \"Regulation of headless isoform expression and function uncharacterized\",\n        \"Structural basis of motor domain processivity on actin bundles not defined\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Demonstrating that PH domain–PtdIns(3,4,5)P3 interaction recruits MYO10 to the plasma membrane and is required for axon outgrowth linked lipid signaling to MYO10 activation and established its role in neuronal polarization.\",\n      \"evidence\": \"shRNA knockdown, PH-domain mutant rescue, and in vivo neocortex radial migration assay in hippocampal neurons\",\n      \"pmids\": [\"22590642\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether PI3K isoform specificity governs MYO10 recruitment not tested\",\n        \"Downstream effectors mediating axon specification after MYO10 activation unidentified\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Showing that MYO10 drives tunneling nanotube formation through the F2 lobe of its FERM domain—independent of integrin or cadherin binding—expanded MYO10 function beyond filopodia to intercellular communication conduits.\",\n      \"evidence\": \"Domain-deletion constructs and vesicle transfer assays in co-cultured CAD cells\",\n      \"pmids\": [\"23886947\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"FERM F2 lobe binding partner that mediates TNT formation not identified\",\n        \"Whether TNT phenotype is relevant in vivo not tested\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Genetic epistasis in macrophages placed MYO10 downstream of Cdc42 for filopodia induction while showing that phagocytic cup formation and motility are MYO10-independent, delineating the boundaries of MYO10 function in innate immune cells.\",\n      \"evidence\": \"Myeloid-specific Cdc42 and Myo10 knockout mice, live confocal imaging, phagocytosis assays\",\n      \"pmids\": [\"28289096\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Signal between Cdc42 activation and MYO10 engagement not identified\",\n        \"Whether filopodia loss affects pathogen sensing in vivo not assessed\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Full-length MYO10 knockout mice revealed essential in vivo roles in neural tube closure, digit separation, and vascular regression, connecting filopodial function to major developmental morphogenesis programs.\",\n      \"evidence\": \"Myo10tm2 reporter knockout mice with MRI, retinal whole mounts, and histology\",\n      \"pmids\": [\"30679680\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Cell-type-specific contributions to neural tube closure not dissected\",\n        \"Whether headless isoform partially compensates in vivo not quantified\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identifying β-TrCP1 and UbcH7 as the E3/E2 pair mediating MYO10 proteasomal degradation, and linking MYO10 overexpression to genomic instability and cGAS/STING inflammatory signaling, established MYO10 as a regulated oncoprotein whose levels must be controlled for genome integrity.\",\n      \"evidence\": \"Co-IP, ubiquitination assays, MYO10 overexpression/depletion in cancer lines and mouse tumor models\",\n      \"pmids\": [\"34524844\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Kinase responsible for degron phosphorylation not identified at this stage\",\n        \"How MYO10 overexpression mechanistically causes micronuclei formation unclear\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Three independent studies in 2022 broadened MYO10's functional scope: stabilization of RACK1 to activate integrin/Src/FAK signaling in colorectal cancer metastasis, maintenance of basement membrane integrity around cancer spheroids, and promotion of transzonal projections in ovarian follicles.\",\n      \"evidence\": \"LC-MS/MS with reciprocal Co-IP and MYO10 KO in CRC cells; RNAi in DCIS xenografts with BM marker imaging; RNAi in granulosa-oocyte complexes with TZP quantification\",\n      \"pmids\": [\"35912545\", \"36283390\", \"35470858\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How MYO10 prevents RACK1 ubiquitination mechanistically is unknown\",\n        \"Whether BM maintenance and invasive functions of MYO10 are context-dependent or cell-intrinsic not resolved\",\n        \"Molecular basis of TZP formation by MYO10 in follicles not characterized\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Mapping the phospho-degron that controls β-TrCP1-mediated MYO10 turnover during mitosis, and showing MYO10 transient accumulation at centrosomes and midbodies, established a cell-cycle-regulated role for MYO10 in faithful chromosome segregation distinct from its interphase filopodial function.\",\n      \"evidence\": \"Degron mutagenesis, phosphorylation site mapping, live MYO10-GFP imaging during mitosis, genomic instability assays\",\n      \"pmids\": [\"37200188\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mitotic kinase phosphorylating the degron not conclusively identified\",\n        \"Centrosomal and midbody binding partners of MYO10 during mitosis unknown\",\n        \"Whether mitotic MYO10 function is motor-dependent not tested\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Demonstrating that the coiled-coil domain is required for sustained tip-directed motility and multiple elongation cycles refined the model from simple tip transport to a processive mechanism involving dimerization-dependent processivity.\",\n      \"evidence\": \"Coiled-coil mutant and tail-truncation constructs with quantitative filopodia length/number analysis and live imaging\",\n      \"pmids\": [\"38043799\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether coiled-coil mediates dimerization or scaffolding not structurally resolved\",\n        \"Cargo carried during elongation cycles not identified\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include the identity of the mitotic kinase phosphorylating the MYO10 degron, the structural basis for MYO10 processivity on bundled actin, whether MYO10's primary role is cortical actin reorganization during filopodia initiation versus membrane tension reduction during elongation, and the molecular mechanism by which MYO10 stabilizes RACK1.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mitotic kinase identity unknown\",\n        \"Cryo-EM or high-resolution structure of MYO10 on actin bundles lacking\",\n        \"Initiation vs. elongation role debated but not conclusively separated\"\n      ]\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, 5, 12, 13]},\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 5, 12]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 8]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [6]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [7, 11]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [7, 11]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"BTRC\",\n      \"UBE2L3\",\n      \"GNB2L1\",\n      \"CDC42\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}