HGNC Approved Gene Symbol: MYO10
Cytogenetic location: 5p15.1 Genomic coordinates (GRCh38): 5:16,661,907-16,936,288 (from NCBI)
By PCR amplification of RNA from porcine and human cell lines and human liver, Bement et al. (1994) identified 8 to 11 putative myosins representing 6 distinct myosin classes. Among the identified myosins was a cDNA encoding MYO10.
Using gel overlays and yeast 2-hybrid screens, Rogers and Strehler (2001) identified MYO10 as a specific Ca(2+)-dependent binding partner for calmodulin-like protein (CLP, or CALML3; 114184). CLP specifically bound to motif 3 of the IQ domain of MYO10, and both proteins colocalized at the cell periphery of mammary carcinoma cells. Rogers and Strehler (2001) concluded that CLP is a specific light chain of MYO10 in vivo.
Phagocytosis is a phosphatidylinositol 3-kinase (PI3K; see 601232)-dependent process in macrophages. Using RT-PCR, Cox et al. (2002) detected Myo10 mRNA in macrophages of diverse mammalian origin. They showed that Myo10 was recruited to phagocytic cups of bovine alveolar macrophages and that recruitment was dependent upon PI3K. Expression of a truncation construct consisting of the Myo10 tail inhibited phagocytosis, whereas expression of the Myo10 tail with a mutation in the second pleckstrin homology domain failed to inhibit phagocytosis. Expression of the Myo10 tail inhibited spreading, but not adhesion, on antibody-coated substrates. The authors concluded that MYO10 provides a molecular link between PI3K and pseudopod extension during phagocytosis.
Using primarily bovine cDNA constructs and cells, Berg and Cheney (2002) found that Myo10 localized to the tips of filopodia and underwent forward and rearward movements within filopodia that corresponded to the movement of phase-dense cargo granules. Overexpression of full-length bovine Myo10, but not truncated forms of Myo10, caused an increase in the number and length of filopodia. Berg and Cheney (2002) concluded that MYO10 is a motor for intrafilopodial motility, and that MYO10 or its cargo may function in filopodial dynamics.
Weber et al. (2004) showed that Xenopus laevis myosin-10 associated with microtubules in vitro and in vivo, and was concentrated at the point where the meiotic spindle contacts the F-actin (see 102610)-rich cortex. Microtubule association was mediated by the MyTH4-FERM domains, which bind directly to purified microtubules. Disruption of Myo10 function disrupted nuclear anchoring, spindle assembly, and spindle-F-actin association. Weber et al. (2004) concluded that myosin-10 has a novel and critically important role during meiosis in integrating the F-actin and microtubule cytoskeletons.
Bohil et al. (2006) found that small interfering RNA-mediated knockdown of MYO10 or overexpression of the coiled-coil region of MYO10 as a dominant-negative caused a dramatic loss of dorsal filopodia in HeLa cells and an increase in cell spreading. Expression of MYO10 in COS-7 fibroblasts, which normally lack dorsal filopodia, induced massive expression of dorsal filopodia, independent of substrate attachment, and reduced cell spreading. A MYO10 construct lacking the integrin-binding FERM domain retained the ability to induce dorsal filopodia, but deletion of the MYTH4-FERM region or the motor domain of MYO10 completely abolished its filopodia-promoting activity. Additional experiments showed that MYO10 acted downstream of CDC42 (116952) and could promote filopodia in the absence of VASP proteins (see VASP; 601703). Bohil et al. (2006) concluded that MYO10 is a molecular motor that functions in filopodia formation.
Using interspecific backcross mapping, Hasson et al. (1996) mapped the Myo10 gene to mouse chromosome 15 in a region that predicted a location of the human homolog on either 5p14-p12 or 8q22-q23. They showed by fluorescence in situ hybridization that human MYO10 maps to 5p15.1-p14.3.
Associations Pending Confirmation
Patel et al. (2018) studied a cohort of 147 patients from 93 families from highly consanguineous populations (Saudi Arabian, Egyptian, and Lebanese) with a diagnosis of microphthalmia, anophthalmia, colobomatous microphthalmia (66 families), Warburg Micro syndrome (4 families) and posterior microphthalmia (23 families). In each family, authors analyzed a panel of 322 genes associated with eye diseases, followed by whole-exome sequencing if the panel did not yield a likely causal mutation. They identified a female patient (10DG0563) from a consanguineous family (F26-M) who had colobomatous microphthalmia (see MCOPCB1, 300345) and was homozygous for a 1-bp duplication (c.1956dup) in the MYO10 gene, causing a frameshift predicted to result in a premature termination codon (Val653CysfsTer35). Her first-cousin parents and an unaffected brother were heterozygous for the duplication, which was not found in another unaffected brother, in an in-house database of 2,369 patients, or in the gnomAD database. RT-PCR showed that the mutant MYO10 did not undergo nonsense-mediated decay.
Bement, W. M., Hasson, T., Wirth, J. A., Cheney, R. E., Mooseker, M. S. Identification and overlapping expression of multiple unconventional myosin genes in vertebrate cell types. Proc. Nat. Acad. Sci. 91: 6549-6553, 1994. Erratum: Proc. Nat. Acad. Sci. 91: 11767, 1994. [PubMed: 8022818] [Full Text: https://doi.org/10.1073/pnas.91.14.6549]
Berg, J. S., Cheney, R. E. Myosin-X is an unconventional myosin that undergoes intrafilopodial motility. Nature Cell Biol. 4: 246-250, 2002. [PubMed: 11854753] [Full Text: https://doi.org/10.1038/ncb762]
Bohil, A. B., Robertson, B. W., Cheney, R. E. Myosin-X is a molecular motor that functions in filopodia formation. Proc. Nat. Acad. Sci. 103: 12411-12416, 2006. [PubMed: 16894163] [Full Text: https://doi.org/10.1073/pnas.0602443103]
Cox, D., Berg, J. S., Cammer, M., Chinegwundoh, J. O., Dale, B. M., Cheney, R. E., Greenberg, S. Myosin X is a downstream effector of PI(3)K during phagocytosis. Nature Cell Biol. 4: 469-477, 2002. [PubMed: 12055636] [Full Text: https://doi.org/10.1038/ncb805]
Hasson, T., Skowron, J. F., Gilbert, D. J., Avraham, K. B., Perry, W. L., Bement, W. M., Anderson, B. L., Sherr, E. H., Chen, Z.-Y., Greene, L. A., Ward, D. C., Corey, D. P., Mooseker, M. S., Copeland, N. G., Jenkins, N. A. Mapping of unconventional myosins in mouse and human. Genomics 36: 431-439, 1996. [PubMed: 8884266] [Full Text: https://doi.org/10.1006/geno.1996.0488]
Patel, N., Khan, A. O., Alsahli, S., Abdel-Salam, G., Nowilaty, S. R., Mansour, A. M., Nabil, A., Al-Owain, M., Sogati, S., Salih, M. A., Kamal, A. M., Alsharif, H., and 14 others. Genetic investigation of 93 families with microphthalmia or posterior microphthalmos. Clin. Genet. 93: 1210-1222, 2018. [PubMed: 29450879] [Full Text: https://doi.org/10.1111/cge.13239]
Rogers, M. S., Strehler, E. E. The tumor-sensitive calmodulin-like protein is a specific light chain of human unconventional myosin X. J. Biol. Chem. 276: 12182-12189, 2001. [PubMed: 11278607] [Full Text: https://doi.org/10.1074/jbc.M010056200]
Weber, K. L., Sokac, A. M., Berg, J. S., Cheney, R. E., Bement, W. M. A microtubule-binding myosin required for nuclear anchoring and spindle assembly. Nature 431: 325-329, 2004. [PubMed: 15372037] [Full Text: https://doi.org/10.1038/nature02834]