Myo15

Summary

Gene Symbol: Myo15
Description: myosin XV
Alias: Myo15a, sh-2, sh2, unconventional myosin-XV, myosin XVA, shaker 2, unconventional myosin-15
Species: mouse
Products:     Myo15

Top Publications

  1. Calderon A, Derr A, Stagner B, Johnson K, Martin G, Noben Trauth K. Cochlear developmental defect and background-dependent hearing thresholds in the Jackson circler (jc) mutant mouse. Hear Res. 2006;221:44-58 pubmed
    ..Genome-wide linkage scans of backcross, intercross, and congenic progeny revealed a complex pattern of genetic and stochastic effects. ..
  2. Caberlotto E, Michel V, Foucher I, Bahloul A, Goodyear R, Pepermans E, et al. Usher type 1G protein sans is a critical component of the tip-link complex, a structure controlling actin polymerization in stereocilia. Proc Natl Acad Sci U S A. 2011;108:5825-30 pubmed publisher
    ..In Ush1g(fl/fl)Myo15-cre(+/-) mice, the loss of sans occurs postnatally and the stereocilia remain cohesive...
  3. Belyantseva I, Boger E, Friedman T. Myosin XVa localizes to the tips of inner ear sensory cell stereocilia and is essential for staircase formation of the hair bundle. Proc Natl Acad Sci U S A. 2003;100:13958-63 pubmed
    Mutations of the gene encoding unconventional myosin XVa are associated with sensorineural deafness in humans (DFNB3) and shaker (Myo15sh2) mice...
  4. Giese A, Tang Y, Sinha G, Bowl M, Goldring A, Parker A, et al. CIB2 interacts with TMC1 and TMC2 and is essential for mechanotransduction in auditory hair cells. Nat Commun. 2017;8:43 pubmed publisher
    ..Here the authors show that protein responsible for Usher syndrome, CIB2, interacts with these channels and is essential for their function and hearing in mice. ..
  5. Hwang C, Guo D, Harris M, Howard O, Mishina Y, Gan L, et al. Role of bone morphogenetic proteins on cochlear hair cell formation: analyses of Noggin and Bmp2 mutant mice. Dev Dyn. 2010;239:505-13 pubmed publisher
    ..Furthermore, Gfi1(cre/+);Bmp2(lox/-) mice are viable and have largely normal hearing. The combined results of Noggin and Bmp2 mutants suggest that Noggin is likely to regulate other Bmps in the cochlea such as Bmp4. ..
  6. Lin Z, Cantos R, Patente M, Wu D. Gbx2 is required for the morphogenesis of the mouse inner ear: a downstream candidate of hindbrain signaling. Development. 2005;132:2309-18 pubmed
    ..However, Gbx2 promotes ventral fates such as the saccule and cochlear duct, possibly by restricting Otx2 expression...
  7. Burton Q, Cole L, Mulheisen M, Chang W, Wu D. The role of Pax2 in mouse inner ear development. Dev Biol. 2004;272:161-75 pubmed
  8. Kelton D, Rauch H. Linkage of open eyelids with linkage group VII of the mouse. J Hered. 1968;59:27-8 pubmed
  9. Fang Q, Indzhykulian A, Mustapha M, Riordan G, Dolan D, Friedman T, et al. The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing. elife. 2015;4: pubmed publisher
    ..Our results show that myosin 15 isoforms can navigate between functionally distinct classes of stereocilia, and are independently required to assemble and then maintain the intricate hair bundle architecture. ..

More Information

Publications56

  1. Bird J, Takagi Y, Billington N, Strub M, Sellers J, Friedman T. Chaperone-enhanced purification of unconventional myosin 15, a molecular motor specialized for stereocilia protein trafficking. Proc Natl Acad Sci U S A. 2014;111:12390-5 pubmed publisher
    b>Unconventional myosin 15 is a molecular motor expressed in inner ear hair cells that transports protein cargos within developing mechanosensory stereocilia...
  2. Sellers J. Myosins: a diverse superfamily. Biochim Biophys Acta. 2000;1496:3-22 pubmed
    ..This review will focus on myosins from class IV, VI, VII, VIII, X, XI, XII, XIII, XIV and XV. In addition, the function of myosin II in non-muscle cells will also be discussed. ..
  3. Weimar W, Lane P, Sidman R. Vibrator (vb): a spinocerebellar system degeneration with autosomal recessive inheritance in mice. Brain Res. 1982;251:357-64 pubmed
  4. Prosser H, Rzadzinska A, Steel K, Bradley A. Mosaic complementation demonstrates a regulatory role for myosin VIIa in actin dynamics of stereocilia. Mol Cell Biol. 2008;28:1702-12 pubmed
    ..Furthermore, myosin VIIa localized at the tips of all abnormally short stereocilia of mice deficient for either myosin XVa or whirlin...
  5. Lelli A, Asai Y, Forge A, Holt J, Géléoc G. Tonotopic gradient in the developmental acquisition of sensory transduction in outer hair cells of the mouse cochlea. J Neurophysiol. 2009;101:2961-73 pubmed publisher
    ..The spatiotemporal expression patterns of myosin 1c and PMCA2 mRNA were correlated with developmental changes in several properties of mechanotransduction. ..
  6. Anniko M. Specific pathology of the stria vascularis in postnatal progressive genetic inner ear disorder. Hear Res. 1982;6:247-58 pubmed
    ..Occasionally such inclusions occurred in marginal cells. In the Shaker-1 (Sh-1) a flattening of intermediate cells occurred but otherwise no pathological changes were found 6--9 weeks after birth...
  7. Grimsley Myers C, Sipe C, Géléoc G, Lu X. The small GTPase Rac1 regulates auditory hair cell morphogenesis. J Neurosci. 2009;29:15859-69 pubmed publisher
    ..Together, these results reveal a critical function of Rac1 in morphogenesis of the auditory sensory epithelium and stereociliary bundle...
  8. Belyantseva I, Boger E, Naz S, Frolenkov G, Sellers J, Ahmed Z, et al. Myosin-XVa is required for tip localization of whirlin and differential elongation of hair-cell stereocilia. Nat Cell Biol. 2005;7:148-56 pubmed
    ..Abnormally short stereocilia bundles that have a diminished staircase are characteristic of the shaker 2 (Myo15a(sh2)) and whirler (Whrn(wi)) strains of deaf mice...
  9. Yoon H, Lee D, Kim M, Bok J. Identification of genes concordantly expressed with Atoh1 during inner ear development. Anat Cell Biol. 2011;44:69-78 pubmed publisher
    ..Here, by reanalyzing archived genetic profiling data, we identified a list of novel genes possibly involved in hair cell differentiation. ..
  10. Lee D, Cahill H, Ryugo D. Effects of congenital deafness in the cochlear nuclei of Shaker-2 mice: an ultrastructural analysis of synapse morphology in the endbulbs of Held. J Neurocytol. 2003;32:229-43 pubmed
    ..to examine further the role of hearing on synapse development, we have studied endbulbs of Held in the shaker-2 ( sh2 ) mouse...
  11. Mburu P, Kikkawa Y, Townsend S, Romero R, Yonekawa H, Brown S. Whirlin complexes with p55 at the stereocilia tip during hair cell development. Proc Natl Acad Sci U S A. 2006;103:10973-8 pubmed
    ..Mutations in the whirlin gene (whirler) and in the myosin XVa gene (shaker2) affect stereocilia development and lead to early ablation of p55 and 4.1R labeling of stereocilia...
  12. Probst F, Fridell R, Raphael Y, Saunders T, Wang A, Liang Y, et al. Correction of deafness in shaker-2 mice by an unconventional myosin in a BAC transgene. Science. 1998;280:1444-7 pubmed
    ..An unconventional myosin gene, Myo15, was discovered by DNA sequencing of this BAC...
  13. Kocher W. [Studies on the genetics and pathology of the development of 8 labyrinth mutants (deaf-waltzer-shaker mutants) in the mouse (Mus musculus)]. Z Vererbungsl. 1960;91:114-40 pubmed
  14. Probst F, Chen K, Zhao Q, Wang A, Friedman T, Lupski J, et al. A physical map of the mouse shaker-2 region contains many of the genes commonly deleted in Smith-Magenis syndrome (del17p11.2p11.2). Genomics. 1999;55:348-52 pubmed
    We report the construction of a physical map of the region of mouse chromosome 11 that encompasses shaker-2 (sh2), a model for the human nonsyndromic deafness DFNB3...
  15. Wakabayashi Y, Takahashi Y, Kikkawa Y, Okano H, Mishima Y, Ushiki T, et al. A novel type of myosin encoded by the mouse deafness gene shaker-2. Biochem Biophys Res Commun. 1998;248:655-9 pubmed
    ..This suggests that the novel myosin gene is a strong candidate for DFNB3. ..
  16. Keats B, Berlin C. Genomics and hearing impairment. Genome Res. 1999;9:7-16 pubmed
    ..TECTA), the transcription factor POU4F3, connexin 26 (GJB2), and two unconventional myosins (MYO7A and MYO15), and four novel proteins (PDS, COCH, DFNA5, DFNB9)...
  17. Pepermans E, Michel V, Goodyear R, Bonnet C, Abdi S, Dupont T, et al. The CD2 isoform of protocadherin-15 is an essential component of the tip-link complex in mature auditory hair cells. EMBO Mol Med. 2014;6:984-92 pubmed publisher
    ..electrophysiological analyses of post-natal hair cell-specific conditional knockout mice (Pcdh15ex38-fl/ex38-fl Myo15-cre+/-) that lose only this isoform after normal hair-bundle development, we show that Pcdh15-CD2 is an essential ..
  18. Kawashima Y, Géléoc G, Kurima K, Labay V, Lelli A, Asai Y, et al. Mechanotransduction in mouse inner ear hair cells requires transmembrane channel-like genes. J Clin Invest. 2011;121:4796-809 pubmed publisher
    ..Our data also suggest that persistent TMC2 expression in vestibular hair cells may preserve vestibular function in humans with hearing loss caused by TMC1 mutations...
  19. Kikkawa Y, Mburu P, Morse S, Kominami R, Townsend S, Brown S. Mutant analysis reveals whirlin as a dynamic organizer in the growing hair cell stereocilium. Hum Mol Genet. 2005;14:391-400 pubmed
    ..We have investigated the function of whirlin and its putative interacting partner, myosin XVa, in the stereocilium using relevant mice mutants...
  20. Carter T, Phillips R. The sex distribution of waved-2, shaker-2 and Rex in the house mouse. Z Indukt Abstamm Vererbungsl. 1953;85:564-78 pubmed
  21. Wakabayashi Y, Kikkawa Y, Matsumoto Y, Shinbo T, Kosugi S, Chou D, et al. Genetic and physical delineation of the region of the mouse deafness mutation shaker-2. Biochem Biophys Res Commun. 1997;234:107-10 pubmed
    ..This covers the entire nonrecombinant region of sh-2 and is therefore useful to facilitate the identification of genes in the sh-2 region. ..
  22. Stepanyan R, Belyantseva I, Griffith A, Friedman T, Frolenkov G. Auditory mechanotransduction in the absence of functional myosin-XVa. J Physiol. 2006;576:801-8 pubmed
    ..In adult shaker 2 mice, a mutation that disables the motor function of myosin-XVa results in profound deafness and abnormally short ..
  23. Clark F. Linkage Relations of Zavadskaia Shaker in the House Mouse (Mus musculus). Proc Natl Acad Sci U S A. 1935;21:247-51 pubmed
  24. Beyer L, Odeh H, Probst F, Lambert E, Dolan D, Camper S, et al. Hair cells in the inner ear of the pirouette and shaker 2 mutant mice. J Neurocytol. 2000;29:227-40 pubmed
    The shaker 2 (sh2) and pirouette (pi) mouse mutants display severe inner ear dysfunction that involves both auditory and vestibular manifestation. Pathology of the stereocilia of hair cells has been found in both mutants...
  25. Webster D, Sobin A, Anniko M. Incomplete maturation of brainstem auditory nuclei in genetically induced early postnatal cochlear degeneration. Acta Otolaryngol. 1986;101:429-38 pubmed
    ..The early cochlear degeneration coincides with the critical period when a normal input from the peripheral receptor organ is necessary for the maturation of the central auditory pathway. ..
  26. Karolyi I, Probst F, Beyer L, Odeh H, Dootz G, Cha K, et al. Myo15 function is distinct from Myo6, Myo7a and pirouette genes in development of cochlear stereocilia. Hum Mol Genet. 2003;12:2797-805 pubmed
    The unconventional myosin genes Myo15, Myo6 and Myo7a are essential for hearing in both humans and mice...
  27. Etournay R, Lepelletier L, Boutet de Monvel J, Michel V, Cayet N, Leibovici M, et al. Cochlear outer hair cells undergo an apical circumference remodeling constrained by the hair bundle shape. Development. 2010;137:1373-83 pubmed publisher
    ..We propose that this remodeling contributes to optimize the mechanical coupling between the basal and apical poles of mature OHCs. ..
  28. Watanabe M, Akiyama N, Manome Y, Hasegawa N. Spontaneous mutant ICR kuru2 might be another shaker-2 deaf mouse. In Vivo. 2012;26:787-91 pubmed
    ..Considering the function that the affected area regulates and previous reports, hearing loss of the examined mouse is attributable to the abnormality of the myoXV gene and this mouse might be another type of shaker-2 deaf mouse. ..
  29. Stepanyan R, Frolenkov G. Fast adaptation and Ca2+ sensitivity of the mechanotransducer require myosin-XVa in inner but not outer cochlear hair cells. J Neurosci. 2009;29:4023-34 pubmed publisher
    ..Here, we examined mechanotransduction in the hair cells of young postnatal shaker 2 mice (Myo15(sh2/sh2))...
  30. Probst F, Camper S. The role of mouse mutants in the identification of human hereditary hearing loss genes. Hear Res. 1999;130:1-6 pubmed
    ..In recent years, the identification of five different mutated genes in the mouse (Pax3, Mitf; Myo7a, Pou4f3, and Myo15) has led directly to the identification of mutations in families with either congenital sensorineural deafness or ..
  31. Choo D, Ward J, Reece A, Dou H, Lin Z, Greinwald J. Molecular mechanisms underlying inner ear patterning defects in kreisler mutants. Dev Biol. 2006;289:308-17 pubmed
    ..The data also identify Gbx2, Dlx5, Wnt2b and Otx2 as key otic genes ultimately affected by perturbation of the kr/mafB-hindbrain pathway. ..
  32. Sobin A, Anniko M, Flock A. Rods of actin filaments in type I hair cells of the Shaker-2 mouse. Arch Otorhinolaryngol. 1982;236:1-6 pubmed
    ..It is concluded that the identical pathology at a cellular level in two different species may indicate a pathologic disorder in a process fundamental to the normal development of this type of hair cell. ..
  33. Kiernan A, Steel K. Mouse homologues for human deafness. Adv Otorhinolaryngol. 2000;56:233-43 pubmed
  34. Oliver T, Berg J, Cheney R. Tails of unconventional myosins. Cell Mol Life Sci. 1999;56:243-57 pubmed
    ..1, Ezrin, Radixin, Moesin) domains, that are present in the tails of otherwise very different myosins as well as a plant kinesin-like protein. Recent progress in the identification of novel unconventional myosins will also be summarized. ..
  35. Manor U, Disanza A, Grati M, Andrade L, Lin H, Di Fiore P, et al. Regulation of stereocilia length by myosin XVa and whirlin depends on the actin-regulatory protein Eps8. Curr Biol. 2011;21:167-72 pubmed publisher
    b>Myosin XVa (MyoXVa) and its cargo whirlin are implicated in deafness and vestibular dysfunction and have been shown to localize at stereocilia tips and to be essential for the elongation of these actin protrusions [1-4]...
  36. Erichsen S, Mikkola M, Sahlin L, Hultcrantz M. Cochlear distribution of Na,K-ATPase and corticosteroid receptors in two mouse strains with congenital hearing disorders. Acta Otolaryngol. 2001;121:794-802 pubmed
    ..The conclusion that reduced Na,K-ATPase levels in both mouse strains may be an important mechanism of the disturbed endolymph production is less controversial. ..
  37. Kanzaki S, Beyer L, Karolyi I, Dolan D, Fang Q, Probst F, et al. Transgene correction maintains normal cochlear structure and function in 6-month-old Myo15a mutant mice. Hear Res. 2006;214:37-44 pubmed
    ..The insertion of a bacterial artificial chromosome (BAC) transgene containing the Myo15a gene into sh2/sh2 zygotes confers hearing capability and abolishes the circling behavior in 1-month-old transgenic ..
  38. Liang Y, Wang A, Belyantseva I, Anderson D, Probst F, Barber T, et al. Characterization of the human and mouse unconventional myosin XV genes responsible for hereditary deafness DFNB3 and shaker 2. Genomics. 1999;61:243-58 pubmed
    ..myosin XV are responsible for congenital profound deafness DFNB3 in humans and deafness and vestibular defects in shaker 2 mice. By combining direct cDNA analyses with a comparison of 95...
  39. Delprat B, Michel V, Goodyear R, Yamasaki Y, Michalski N, El Amraoui A, et al. Myosin XVa and whirlin, two deafness gene products required for hair bundle growth, are located at the stereocilia tips and interact directly. Hum Mol Genet. 2005;14:401-10 pubmed
    Defects in myosin XVa and the PDZ domain-containing protein, whirlin, underlie deafness in humans and mice. Hair bundles of mutant mice defective for either protein have abnormally short stereocilia...
  40. Zheng L, Zheng J, Whitlon D, Garcia Anoveros J, Bartles J. Targeting of the hair cell proteins cadherin 23, harmonin, myosin XVa, espin, and prestin in an epithelial cell model. J Neurosci. 2010;30:7187-201 pubmed publisher
    ..The unconventional myosin motor myosin XVa accumulated at the tips of espin-elongated microvilli, by analogy to its location in stereocilia, whereas myosin ..
  41. Anderson D, Probst F, Belyantseva I, Fridell R, Beyer L, Martin D, et al. The motor and tail regions of myosin XV are critical for normal structure and function of auditory and vestibular hair cells. Hum Mol Genet. 2000;9:1729-38 pubmed
    ..profound congenital deafness in humans and both deafness and vestibular dysfunction in mice homozygous for the shaker 2 and shaker 2(J) alleles...
  42. Bossi G, Booth S, Clark R, Davis E, Liesner R, Richards K, et al. Normal lytic granule secretion by cytotoxic T lymphocytes deficient in BLOC-1, -2 and -3 and myosins Va, VIIa and XV. Traffic. 2005;6:243-51 pubmed
    ..These results reveal differences in the protein machinery required for biogenesis and/or secretion of lysosome-related organelles in CTL and melanocytes...
  43. Liang Y, Wang A, Probst F, Arhya I, Barber T, Chen K, et al. Genetic mapping refines DFNB3 to 17p11.2, suggests multiple alleles of DFNB3, and supports homology to the mouse model shaker-2. Am J Hum Genet. 1998;62:904-15 pubmed
    ..On the basis of conserved synteny, mouse deafness mutations shaker-2 (sh2) and sh2J are proposed as models of DFNB3. Genetic mapping has refined sh2 to a 0.6-cM interval of chromosome 11...
  44. Delmaghani S, Defourny J, Aghaie A, Beurg M, Dulon D, Thelen N, et al. Hypervulnerability to Sound Exposure through Impaired Adaptive Proliferation of Peroxisomes. Cell. 2015;163:894-906 pubmed publisher
    ..Our results reveal that the antioxidant activity of peroxisomes protects the auditory system against noise-induced damage. ..
  45. Mustapha M, Beyer L, Izumikawa M, Swiderski D, Dolan D, Raphael Y, et al. Whirler mutant hair cells have less severe pathology than shaker 2 or double mutants. J Assoc Res Otolaryngol. 2007;8:329-37 pubmed
    ..b>Shaker 2 (sh2) mice have a mutation in the motor domain of MYOSIN XV and exhibit congenital deafness and circling behavior,..
  46. Riccomagno M, Martinu L, Mulheisen M, Wu D, Epstein D. Specification of the mammalian cochlea is dependent on Sonic hedgehog. Genes Dev. 2002;16:2365-78 pubmed
    ..Taken together, our data support a model whereby auditory cell fates in the otic vesicle are established by the direct action of Shh. ..
  47. Roeseler D, Sachdev S, Buckley D, Joshi T, Wu D, Xu D, et al. Elongation factor 1 alpha1 and genes associated with Usher syndromes are downstream targets of GBX2. PLoS ONE. 2012;7:e47366 pubmed publisher
    ..Taken together, our studies show that GBX2 plays a dynamic role in development and diseases. ..