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Gene Review

MYO6  -  myosin VI

Homo sapiens

Synonyms: DFNA22, DFNB37, KIAA0389, Unconventional myosin-6, Unconventional myosin-VI
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Disease relevance of MYO6


Psychiatry related information on MYO6


High impact information on MYO6

  • Myosin VI can move along actin filaments to serve as a transport motor [7].
  • We show that sv encodes an unconventional myosin heavy chain, myosin VI, which is expressed within the sensory hair cells of the inner ear, and appears to be required for maintaining their structural integrity [8].
  • The recently solved structure of the myosin VI motor demonstrates that the unique insert at the end of the motor is responsible for the reversal of the normal myosin directionality [9].
  • Myosin VI: a structural role in actin organization important for protein and organelle localization and trafficking [10].
  • We hypothesize that the main function of myosin VI is to bind tightly to actin, stabilizing actin cytoskeletal structures and linking actin structures to membranes and protein complexes [10].

Biological context of MYO6


Anatomical context of MYO6

  • Taken together, these data indicate that myosin VI and Dab2 facilitate CFTR endocytosis by a mechanism that requires actin filaments [13].
  • A null mutation in myosin VI in the congenitally deaf Snell's waltzer mice (Myo6(sv)) results in fusion of stereocilia and subsequent progressive loss of hair cells, beginning soon after birth, thus reinforcing the vital role of cytoskeletal proteins in inner ear hair cells [14].
  • Myo6 participates in two steps of endocytic trafficking; it is recruited to both clathrin-coated pits and to ensuing uncoated endocytic vesicles (UCV) [15].
  • These data suggest that myo6 is an accessory protein required for the efficient transportation of nascent endocytic vesicles from the actin-rich peripheries of epithelial cells, allowing for timely fusion of endocytic vesicles with the early endosome [16].
  • Overexpression of GFP-M6tail had no effect on a variety of organelle markers; however, GFP-M6tail displaced the endogenous myo6 from nascent vesicles and resulted in a significant delay in transferrin uptake [16].

Associations of MYO6 with chemical compounds


Physical interactions of MYO6

  • The present findings suggest that myosin VI plays a role in transporting DOC-2/DAB2, a Ras cascade signaling molecule, thus involved in Ras signaling pathways [19].
  • In a yeast 2-hybrid screen we identified optineurin as a binding partner for myosin VI at the Golgi complex and confirmed this interaction in a range of protein interaction studies [4].
  • LMTK2 binds to the WWY site in the C-terminal myosin VI tail, the same site as the endocytic adaptor protein Dab2 [20].

Enzymatic interactions of MYO6

  • In A431 cells in which cell surface ruffling was stimulated by EGF, myosin VI was phosphorylated and recruited into the newly formed ruffles along with ezrin and myosin V [21].

Regulatory relationships of MYO6


Other interactions of MYO6


Analytical, diagnostic and therapeutic context of MYO6


  1. MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice, is mutated in autosomal dominant nonsyndromic hearing loss. Melchionda, S., Ahituv, N., Bisceglia, L., Sobe, T., Glaser, F., Rabionet, R., Arbones, M.L., Notarangelo, A., Di Iorio, E., Carella, M., Zelante, L., Estivill, X., Avraham, K.B., Gasparini, P. Am. J. Hum. Genet. (2001) [Pubmed]
  2. Lessons from border cell migration in the Drosophila ovary: A role for myosin VI in dissemination of human ovarian cancer. Yoshida, H., Cheng, W., Hung, J., Montell, D., Geisbrecht, E., Rosen, D., Liu, J., Naora, H. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  3. Characterization of Amoeba proteus myosin VI immunoanalog. Dominik, M., Kłopocka, W., Pomorski, P., Kocik, E., Redowicz, M.J. Cell Motil. Cytoskeleton (2005) [Pubmed]
  4. Optineurin links myosin VI to the Golgi complex and is involved in Golgi organization and exocytosis. Sahlender, D.A., Roberts, R.C., Arden, S.D., Spudich, G., Taylor, M.J., Luzio, J.P., Kendrick-Jones, J., Buss, F. J. Cell Biol. (2005) [Pubmed]
  5. A Novel Role of Myosin VI in Human Prostate Cancer. Dunn, T.A., Chen, S., Faith, D.A., Hicks, J.L., Platz, E.A., Chen, Y., Ewing, C.M., Sauvageot, J., Isaacs, W.B., De Marzo, A.M., Luo, J. Am. J. Pathol. (2006) [Pubmed]
  6. Regulation of myosin-VI targeting to endocytic compartments. Dance, A.L., Miller, M., Seragaki, S., Aryal, P., White, B., Aschenbrenner, L., Hasson, T. Traffic (2004) [Pubmed]
  7. Converting a motor to an anchor. Miller, K.G. Cell (2004) [Pubmed]
  8. The mouse Snell's waltzer deafness gene encodes an unconventional myosin required for structural integrity of inner ear hair cells. Avraham, K.B., Hasson, T., Steel, K.P., Kingsley, D.M., Russell, L.B., Mooseker, M.S., Copeland, N.G., Jenkins, N.A. Nat. Genet. (1995) [Pubmed]
  9. What can myosin VI do in cells? Sweeney, H.L., Houdusse, A. Curr. Opin. Cell Biol. (2007) [Pubmed]
  10. Myosin VI: a structural role in actin organization important for protein and organelle localization and trafficking. Frank, D.J., Noguchi, T., Miller, K.G. Curr. Opin. Cell Biol. (2004) [Pubmed]
  11. Mutations of MYO6 are associated with recessive deafness, DFNB37. Ahmed, Z.M., Morell, R.J., Riazuddin, S., Gropman, A., Shaukat, S., Ahmad, M.M., Mohiddin, S.A., Fananapazir, L., Caruso, R.C., Husnain, T., Khan, S.N., Riazuddin, S., Griffith, A.J., Friedman, T.B., Wilcox, E.R. Am. J. Hum. Genet. (2003) [Pubmed]
  12. Characterization of unconventional MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice. Avraham, K.B., Hasson, T., Sobe, T., Balsara, B., Testa, J.R., Skvorak, A.B., Morton, C.C., Copeland, N.G., Jenkins, N.A. Hum. Mol. Genet. (1997) [Pubmed]
  13. Myosin VI regulates endocytosis of the cystic fibrosis transmembrane conductance regulator. Swiatecka-Urban, A., Boyd, C., Coutermarsh, B., Karlson, K.H., Barnaby, R., Aschenbrenner, L., Langford, G.M., Hasson, T., Stanton, B.A. J. Biol. Chem. (2004) [Pubmed]
  14. Unconventional myosins and the genetics of hearing loss. Friedman, T.B., Sellers, J.R., Avraham, K.B. Am. J. Med. Genet. (1999) [Pubmed]
  15. Binding of internalized receptors to the PDZ domain of GIPC/synectin recruits myosin VI to endocytic vesicles. Naccache, S.N., Hasson, T., Horowitz, A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  16. Myo6 facilitates the translocation of endocytic vesicles from cell peripheries. Aschenbrenner, L., Lee, T., Hasson, T. Mol. Biol. Cell (2003) [Pubmed]
  17. Cargo-Binding Makes a Wild-Type Single-Headed Myosin-VI Move Processively. Iwaki, M., Tanaka, H., Iwane, A.H., Katayama, E., Ikebe, M., Yanagida, T. Biophys. J. (2006) [Pubmed]
  18. Myosin VI altered at threonine 406 stabilizes actin filaments in vivo. Naccache, S.N., Hasson, T. Cell Motil. Cytoskeleton (2006) [Pubmed]
  19. DOC-2/DAB2 is the binding partner of myosin VI. Inoue, A., Sato, O., Homma, K., Ikebe, M. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  20. Myosin VI and its interacting protein LMTK2 regulate tubule formation and transport to the endocytic recycling compartment. Chibalina, M.V., Seaman, M.N., Miller, C.C., Kendrick-Jones, J., Buss, F. J. Cell. Sci. (2007) [Pubmed]
  21. The localization of myosin VI at the golgi complex and leading edge of fibroblasts and its phosphorylation and recruitment into membrane ruffles of A431 cells after growth factor stimulation. Buss, F., Kendrick-Jones, J., Lionne, C., Knight, A.E., Côté, G.P., Paul Luzio, J. J. Cell Biol. (1998) [Pubmed]
  22. Nuclear myosin VI enhances RNA polymerase II-dependent transcription. Vreugde, S., Ferrai, C., Miluzio, A., Hauben, E., Marchisio, P.C., Crippa, M.P., Bussi, M., Biffo, S. Mol. Cell (2006) [Pubmed]
  23. Genomic structure of the human unconventional myosin VI gene. Ahituv, N., Sobe, T., Robertson, N.G., Morton, C.C., Taggart, R.T., Avraham, K.B. Gene (2000) [Pubmed]
  24. Myosin VI is an actin-based motor that moves backwards. Wells, A.L., Lin, A.W., Chen, L.Q., Safer, D., Cain, S.M., Hasson, T., Carragher, B.O., Milligan, R.A., Sweeney, H.L. Nature (1999) [Pubmed]
  25. Myosin VI: cellular functions and motor properties. Roberts, R., Lister, I., Schmitz, S., Walker, M., Veigel, C., Trinick, J., Buss, F., Kendrick-Jones, J. Philos. Trans. R. Soc. Lond., B, Biol. Sci. (2004) [Pubmed]
  26. Novel myosin VI isoform is abundantly expressed in retina. Breckler, J., Au, K., Cheng, J., Hasson, T., Burnside, B. Exp. Eye Res. (2000) [Pubmed]
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