Affinage

MYO10

Unconventional myosin-X · UniProt Q9HD67

Length
2058 aa
Mass
237.3 kDa
Annotated
2026-04-29
20 papers in source corpus 14 papers cited in narrative 15 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

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).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2006 High

    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

    PMID:16371656

    Open questions at the time
    • 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
  2. 2012 High

    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

    PMID:22590642

    Open questions at the time
    • Whether PI3K isoform specificity governs MYO10 recruitment not tested
    • Downstream effectors mediating axon specification after MYO10 activation unidentified
  3. 2013 High

    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

    PMID:23886947

    Open questions at the time
    • FERM F2 lobe binding partner that mediates TNT formation not identified
    • Whether TNT phenotype is relevant in vivo not tested
  4. 2017 High

    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

    PMID:28289096

    Open questions at the time
    • Signal between Cdc42 activation and MYO10 engagement not identified
    • Whether filopodia loss affects pathogen sensing in vivo not assessed
  5. 2019 High

    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

    PMID:30679680

    Open questions at the time
    • Cell-type-specific contributions to neural tube closure not dissected
    • Whether headless isoform partially compensates in vivo not quantified
  6. 2021 High

    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

    PMID:34524844

    Open questions at the time
    • Kinase responsible for degron phosphorylation not identified at this stage
    • How MYO10 overexpression mechanistically causes micronuclei formation unclear
  7. 2022 High

    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

    PMID:35470858 PMID:35912545 PMID:36283390

    Open questions at the time
    • 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
  8. 2023 High

    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

    PMID:37200188

    Open questions at the time
    • 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
  9. 2023 High

    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

    PMID:38043799

    Open questions at the time
    • Whether coiled-coil mediates dimerization or scaffolding not structurally resolved
    • Cargo carried during elongation cycles not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • 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.
  • 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

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0003774 cytoskeletal motor activity 3 GO:0008289 lipid binding 1
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-1640170 Cell Cycle 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-1266738 Developmental Biology 1
Partners
BTRCCDC42GNB2L1UBE2L3

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 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. Live cell imaging of GFP-tagged full-length vs. headless Myo10 constructs in neuronal CAD cells Journal of cell science High 16371656
2006 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. Immunoblotting, immunofluorescence, GFP-construct localization in CAD cells and mouse brain Journal of cell science Medium 16371656 30679680
2012 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. Immunofluorescence, shRNA knockdown, GFP-tagged Myo10 PH-domain mutant expression in hippocampal neurons, in vivo neocortex radial migration assay PloS one High 22590642
2013 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. Myo10 overexpression/domain-deletion constructs, vesicle transfer assays in co-cultured CAD cells Journal of cell science High 23886947
2014 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. shRNA knockdown, wound healing assay, Golgi polarity staining, cell adhesion assay, N-cadherin rescue in NLT cells In vitro cellular & developmental biology. Animal Medium 25491426
2017 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. Myeloid-restricted Cdc42 and Myo10 knockout mice, spinning disk confocal live imaging, phagocytosis assays The Journal of biological chemistry High 28289096
2019 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. Myo10 reporter knockout mice (Myo10tm2), MRI, retinal whole-mount preparations, histology Scientific reports High 30679680
2021 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. Co-immunoprecipitation, ubiquitination assays, MYO10 overexpression/depletion in cancer cell lines and mouse tumor models, cGAS/STING pathway readouts Science advances High 34524844
2022 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. LC-MS/MS proteomics, co-immunoprecipitation, MYO10 knockout in CRC cells, Western blot for RACK1 ubiquitination, in vitro and in vivo metastasis assays Cancer science High 35912545
2022 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. MYO10 depletion by RNAi, human DCIS xenografts in mice, 3D spheroid culture, immunofluorescence for BM markers, live imaging Developmental cell High 36283390
2022 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. Immunofluorescence localization in mouse and human follicles, RNAi depletion in granulosa cell-oocyte complexes, quantitative TZP analysis Biology of reproduction Medium 35470858
2023 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. Degron mutagenesis, phosphorylation site mapping, cell fractionation, live imaging of MYO10-GFP during mitosis, flow cytometry, genomic instability assays Cell reports High 37200188
2023 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. GFP-tagged Myo10 tail-truncation and coiled-coil mutant constructs, filopodia length/number quantification, live cell imaging The Journal of biological chemistry High 38043799
2025 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. Site-directed mutagenesis of actin-binding interface, quantitative filopodia assays (number, length, tip intensity), live imaging of Myo10-jd in multiple cell lines bioRxivpreprint Medium bio_10.1101_2025.05.29.656896
2025 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. Lentiviral shRNA knockdown, wound healing assay, filopodia quantification, laminin adhesion spreading assay microPublication biology Medium 41050330

Source papers

Stage 0 corpus · 20 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Myo10 is a key regulator of TNT formation in neuronal cells. Journal of cell science 143 23886947
2015 NF-κB-mediated miR-124 suppresses metastasis of non-small-cell lung cancer by targeting MYO10. Oncotarget 72 25749519
2006 Myo10 in brain: developmental regulation, identification of a headless isoform and dynamics in neurons. Journal of cell science 69 16371656
2020 Circ-calm4 Serves as an miR-337-3p Sponge to Regulate Myo10 (Myosin 10) and Promote Pulmonary Artery Smooth Muscle Proliferation. Hypertension (Dallas, Tex. : 1979) 62 32008463
2017 Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion. The Journal of biological chemistry 47 28289096
2015 MiR-340 suppresses cell migration and invasion by targeting MYO10 in breast cancer. Oncology reports 42 26573744
2022 MYO10-filopodia support basement membranes at pre-invasive tumor boundaries. Developmental cell 27 36283390
2020 LncRNA SNHG7 enhances chemoresistance in neuroblastoma through cisplatin-induced autophagy by regulating miR-329-3p/MYO10 axis. European review for medical and pharmacological sciences 27 32329857
2021 MYO10 drives genomic instability and inflammation in cancer. Science advances 23 34524844
2012 PtdIns (3,4,5) P3 recruitment of Myo10 is essential for axon development. PloS one 20 22590642
2018 miR-129 inhibits tumor growth and potentiates chemosensitivity of neuroblastoma by targeting MYO10. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 19 29864913
2022 MYO10 contributes to the malignant phenotypes of colorectal cancer via RACK1 by activating integrin/Src/FAK signaling. Cancer science 16 35912545
2022 MYO10 promotes transzonal projection-dependent germ line-somatic contact during mammalian folliculogenesis†. Biology of reproduction 14 35470858
2019 Protease activated receptor 2 mediates tryptase-induced cell migration through MYO10 in colorectal cancer. American journal of cancer research 12 31598400
2019 Phenotypic analysis of Myo10 knockout (Myo10tm2/tm2) mice lacking full-length (motorized) but not brain-specific headless myosin X. Scientific reports 11 30679680
2023 MYO10 regulates genome stability and cancer inflammation through mediating mitosis. Cell reports 6 37200188
2014 Myo10 is required for neurogenic cell adhesion and migration. In vitro cellular & developmental biology. Animal 6 25491426
2023 Myo10 tail is crucial for promoting long filopodia. The Journal of biological chemistry 3 38043799
2013 Cloning, characterization, and promoter analysis of mouse Myo10 gene. Nucleosides, nucleotides & nucleic acids 1 23742061
2025 Cells stably expressing shRNA against MYO10 display altered cell motility. microPublication biology 0 41050330