Genomes and Genes
Gene Symbol: Myo6
Description: myosin VI
Alias: BC029719, Tlc, unconventional myosin-VI, Snell's waltzer, tailchaser, unconventional myosin-6
- Lewis M, Quint E, Glazier A, Fuchs H, de Angelis M, Langford C, et al. An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice. Nat Genet. 2009;41:614-8 pubmed publisher..This is the first microRNA found associated with deafness, and diminuendo represents a model for understanding and potentially moderating progressive hair cell degeneration in hearing loss more generally. ..
- Inoue A, Sato O, Homma K, Ikebe M. DOC-2/DAB2 is the binding partner of myosin VI. Biochem Biophys Res Commun. 2002;292:300-7 pubmed..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. ..
- Wu H, Nash J, Zamorano P, Garner C. Interaction of SAP97 with minus-end-directed actin motor myosin VI. Implications for AMPA receptor trafficking. J Biol Chem. 2002;277:30928-34 pubmed..These data suggest that SAP97 may serve as a molecular link between GluR1 and the actin-dependent motor protein myosin VI during the dynamic translocation of AMPA receptors to and from the postsynaptic plasma membrane. ..
- Sakaguchi H, Tokita J, Naoz M, Bowen Pope D, Gov N, Kachar B. Dynamic compartmentalization of protein tyrosine phosphatase receptor Q at the proximal end of stereocilia: implication of myosin VI-based transport. Cell Motil Cytoskeleton. 2008;65:528-38 pubmed publisher..Our results suggest that PTPRQ and myosin VI form a complex that dynamically maintains the organization of the cell surface coat at the stereocilia base and helps maintain the structure of the overall stereocilia bundle. ..
- Hertzano R, Montcouquiol M, Rashi Elkeles S, Elkon R, Yücel R, Frankel W, et al. Transcription profiling of inner ears from Pou4f3(ddl/ddl) identifies Gfi1 as a target of the Pou4f3 deafness gene. Hum Mol Genet. 2004;13:2143-53 pubmed..These results identify Gfi1 as the first downstream target of a hair cell specific transcription factor and suggest that outer hair cell degeneration in Pou4f3 mutants is largely or entirely a result of the loss of expression of Gfi1. ..
- Friedman L, Dror A, Mor E, Tenne T, Toren G, Satoh T, et al. MicroRNAs are essential for development and function of inner ear hair cells in vertebrates. Proc Natl Acad Sci U S A. 2009;106:7915-20 pubmed publisher..Our data support the hypothesis that inner ear tissue differentiation and maintenance are regulated and controlled by conserved sets of cell-specific miRNAs in both mouse and zebrafish. ..
- Adato A, Vreugde S, Joensuu T, Avidan N, Hamalainen R, Belenkiy O, et al. USH3A transcripts encode clarin-1, a four-transmembrane-domain protein with a possible role in sensory synapses. Eur J Hum Genet. 2002;10:339-50 pubmed
- Kiernan A, Zalzman M, Fuchs H, Hrabe de Angelis M, Balling R, Steel K, et al. Tailchaser (Tlc): a new mouse mutation affecting hair bundle differentiation and hair cell survival. J Neurocytol. 1999;28:969-85 pubmed..The pathology and genetic mapping of the first of these new mutants, tailchaser (Tlc), is described here...
- Hayashi T, Cunningham D, Bermingham McDonogh O. Loss of Fgfr3 leads to excess hair cell development in the mouse organ of Corti. Dev Dyn. 2007;236:525-33 pubmed..Thus, in addition to controlling the fate decision between pillar cells and Deiters' cells, we find that Fgfr3 also regulates the width of the sensory epithelium...
- Naccache S, Hasson T, Horowitz A. Binding of internalized receptors to the PDZ domain of GIPC/synectin recruits myosin VI to endocytic vesicles. Proc Natl Acad Sci U S A. 2006;103:12735-40 pubmedMyosin VI (myo6) is the only actin-based molecular motor that translocates along actin filaments toward the minus end...
- Yano H, Ninan I, Zhang H, Milner T, Arancio O, Chao M. BDNF-mediated neurotransmission relies upon a myosin VI motor complex. Nat Neurosci. 2006;9:1009-18 pubmed..Myosin VI (Myo6) is a minus end-directed actin-based motor found in neurons that express Trk receptors...
- Gotoh N, Yan Q, Du Z, Biemesderfer D, Kashgarian M, Mooseker M, et al. Altered renal proximal tubular endocytosis and histology in mice lacking myosin-VI. Cytoskeleton (Hoboken). 2010;67:178-92 pubmed publisherMyosin VI (Myo6) is an actin-based molecular motor involved in clathrin-mediated endocytosis that is highly expressed in the renal proximal tubule brush border...
- Jones C, Roper V, Foucher I, Qian D, Banizs B, Petit C, et al. Ciliary proteins link basal body polarization to planar cell polarity regulation. Nat Genet. 2008;40:69-77 pubmed..Thus, our data uncover a distinct requirement for ciliary genes in basal body positioning and morphological polarization during PCP regulation. ..
- Tamaki K, Kamakura M, Nakamichi N, Taniura H, Yoneda Y. Upregulation of Myo6 expression after traumatic stress in mouse hippocampus. Neurosci Lett. 2008;433:183-7 pubmed publisher..The actin-based molecular motor protein myosin VI (Myo6) was identified as a gene markedly upregulated by traumatic stress in the mouse hippocampus 24h after WIRS...
- Collaco A, Jakab R, Hegan P, Mooseker M, Ameen N. Alpha-AP-2 directs myosin VI-dependent endocytosis of cystic fibrosis transmembrane conductance regulator chloride channels in the intestine. J Biol Chem. 2010;285:17177-87 pubmed publisher..The findings support alpha-AP-2 in directing myosin VI-dependent endocytosis of CFTR and a requirement for myosin VI in membrane invagination and coated pit formation in enterocytes. ..
- Hayashi T, Ray C, Younkins C, Bermingham McDonogh O. Expression patterns of FGF receptors in the developing mammalian cochlea. Dev Dyn. 2010;239:1019-26 pubmed publisher..We compare the receptor expression pattern to markers of the sensory domain (p27kip1) and the early hair cells (math1). ..
- Warner C, Stewart A, Luzio J, Steel K, Libby R, Kendrick Jones J, et al. Loss of myosin VI reduces secretion and the size of the Golgi in fibroblasts from Snell's waltzer mice. EMBO J. 2003;22:569-79 pubmed..Rescue experiments showed that fully functional myosin VI was able to restore Golgi complex morphology and protein secretion in Snell's waltzer cells to the same level as that observed in wild-type cells. ..
- Wallis D, Hamblen M, Zhou Y, Venken K, Schumacher A, Grimes H, et al. The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival. Development. 2003;130:221-32 pubmed..Hence, Gfi1 is expressed in the developing nervous system, is required for inner ear hair cell differentiation, and its loss causes programmed cell death. ..
- Melchionda S, Ahituv N, Bisceglia L, Sobe T, Glaser F, Rabionet R, et al. MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice, is mutated in autosomal dominant nonsyndromic hearing loss. Am J Hum Genet. 2001;69:635-40 pubmedMutations in the unconventional myosin VI gene, Myo6, are associated with deafness and vestibular dysfunction in the Snell's waltzer (sv) mouse. The corresponding human gene, MYO6, is located on chromosome 6q13...
- Bermingham N, Hassan B, Price S, Vollrath M, Ben Arie N, Eatock R, et al. Math1: an essential gene for the generation of inner ear hair cells. Science. 1999;284:1837-41 pubmed..Embryonic Math1-null mice failed to generate cochlear and vestibular hair cells. This gene is thus required for the genesis of hair cells...
- Arden S, Puri C, Au J, Kendrick Jones J, Buss F. Myosin VI is required for targeted membrane transport during cytokinesis. Mol Biol Cell. 2007;18:4750-61 pubmed..Our results suggest that myosin VI has novel functions in mitosis and that it plays an essential role in targeted membrane transport during cytokinesis. ..
- Hertzano R, Shalit E, Rzadzinska A, Dror A, Song L, Ron U, et al. A Myo6 mutation destroys coordination between the myosin heads, revealing new functions of myosin VI in the stereocilia of mammalian inner ear hair cells. PLoS Genet. 2008;4:e1000207 pubmed publisher..Here, we show that a missense mutation in this molecular motor in an ENU-generated mouse model, Tailchaser, disrupts myosin VI function...
- 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...
- Marcotti W, Corns L, Goodyear R, Rzadzinska A, Avraham K, Steel K, et al. The acquisition of mechano-electrical transducer current adaptation in auditory hair cells requires myosin VI. J Physiol. 2016;594:3667-81 pubmed publisher..Mutations in Myo6, the gene encoding the (F-actin) minus end-directed unconventional myosin, myosin VI, cause hereditary deafness in ..
- Masters T, Tumbarello D, Chibalina M, Buss F. MYO6 Regulates Spatial Organization of Signaling Endosomes Driving AKT Activation and Actin Dynamics. Cell Rep. 2017;19:2088-2101 pubmed publisher..Myosin VI (MYO6) and twoÂ ofÂ its cargo adaptor proteins, GIPC and TOM1/TOM1L2, localize to these peripheral endosomes and ..
- Jones C, Qian D, Kim S, Li S, Ren D, Knapp L, et al. Ankrd6 is a mammalian functional homolog of Drosophila planar cell polarity gene diego and regulates coordinated cellular orientation in the mouse inner ear. Dev Biol. 2014;395:62-72 pubmed publisher..Together, these results indicated that mAnkrd6 is a functional homolog of the Drosophila diego gene for mammalian PCP regulation and act to suppress canonical Wnt signaling. ..
- Karolczak J, Sobczak M, Skowronek K, RÄ™dowicz M. A Kinase Anchoring Protein 9 Is a Novel Myosin VI Binding Partner That Links Myosin VI with the PKA Pathway in Myogenic Cells. Biomed Res Int. 2015;2015:816019 pubmed publisher..We postulate that this novel interaction linking MVI with the PKA pathway could be important for targeting AKAP9-PKA complex within cells and/or providing PKA to phosphorylate MVI tail domain. ..
- Coate T, Spita N, Zhang K, Isgrig K, Kelley M. Neuropilin-2/Semaphorin-3F-mediated repulsion promotes inner hair cell innervation by spiral ganglion neurons. elife. 2015;4: pubmed publisher..These results suggest a model in which cochlear innervation patterns by type I SGNs are determined, at least in part, through a Semaphorin-3F-mediated inhibitory signal that impedes processes from extending beyond the IHC region. ..
- Liu M, Horowitz A. A PDZ-binding motif as a critical determinant of Rho guanine exchange factor function and cell phenotype. Mol Biol Cell. 2006;17:1880-7 pubmed..We found that the activity level of JNK, which mediates transcriptional regulation downstream of RhoA, is elevated in a Syx2-dependent manner in these cells, possibly contributing to their tumorigenicity. ..
- Munnamalai V, Fekete D. Notch-Wnt-Bmp crosstalk regulates radial patterning in the mouse cochlea in a spatiotemporal manner. Development. 2016;143:4003-4015 pubmed..In conclusion, Wnt signaling in the cochlea influences patterning through complex crosstalk with the Notch and Bmp pathways at several stages of embryonic development. ..
- Wakaoka T, Motohashi T, Hayashi H, Kuze B, Aoki M, Mizuta K, et al. Tracing Sox10-expressing cells elucidates the dynamic development of the mouse inner ear. Hear Res. 2013;302:17-25 pubmed publisher..Further analyzing the Sox10-IRES-Venus mice would provide important information to better understand the development of the inner ear...
- Zhang Y, Xie S, Zhou Y, Xie Y, Liu P, Sun M, et al. H3K36 histone methyltransferase Setd2 is required for murine embryonic stem cell differentiation toward endoderm. Cell Rep. 2014;8:1989-2002 pubmed publisher..These results indicate that Setd2 controls the primitive endoderm differentiation of mESCs by regulating the Fgfr3-Erk signaling. ..
- Labosky P, Winnier G, Sasaki H, Blessing M, Hogan B. The chromosomal mapping of four genes encoding winged helix proteins expressed early in mouse development. Genomics. 1996;34:241-5 pubmed..Since Mf3 is located in a region of Chromosome 9 containing many well-characterized mouse mutations such as short ear (se), ashen (ash), and dilute (d), we have analyzed deletion mutants to determine the location of Mf3 more precisely. ..
- Geller S, Guerin K, Visel M, Pham A, Lee E, Dror A, et al. CLRN1 is nonessential in the mouse retina but is required for cochlear hair cell development. PLoS Genet. 2009;5:e1000607 pubmed publisher..If CLRN1 expression in humans is comparable to the expression pattern observed in mice, this is the first report of an inner retinal protein that, when mutated, causes retinal degeneration. ..
- Lanahan A, Hermans K, Claes F, Kerley Hamilton J, Zhuang Z, Giordano F, et al. VEGF receptor 2 endocytic trafficking regulates arterial morphogenesis. Dev Cell. 2010;18:713-24 pubmed publisher..This key event in VEGF signaling occurs at an intracellular site and is regulated by a novel endosomal trafficking-dependent process. ..
- Hertzano R, Dror A, Montcouquiol M, Ahmed Z, Ellsworth B, Camper S, et al. Lhx3, a LIM domain transcription factor, is regulated by Pou4f3 in the auditory but not in the vestibular system. Eur J Neurosci. 2007;25:999-1005 pubmed..This is the first example of a hair cell-specific gene expressed both in auditory and in vestibular hair cells, with differential regulation of expression in these two closely related systems. ..
- Karolczak J, Pavlyk I, Majewski Å, Sobczak M, Niewiadomski P, Rzhepetskyy Y, et al. Involvement of unconventional myosin VI in myoblast function and myotube formation. Histochem Cell Biol. 2015;144:21-38 pubmed publisherThe important role of unconventional myosin VI (MVI) in skeletal and cardiac muscle has been recently postulated (Karolczak et al. in Histochem Cell Biol 139:873-885, 2013)...
- Walsh T, Shahin H, Elkan Miller T, Lee M, Thornton A, Roeb W, et al. Whole exome sequencing and homozygosity mapping identify mutation in the cell polarity protein GPSM2 as the cause of nonsyndromic hearing loss DFNB82. Am J Hum Genet. 2010;87:90-4 pubmed publisher..Identification of GPSM2 as essential to the development of normal hearing suggests dysregulation of cell polarity as a mechanism underlying hearing loss. ..
- Zorca C, Kim L, Kim Y, Krause M, Zenklusen D, Spilianakis C, et al. Myosin VI regulates gene pairing and transcriptional pause release in T cells. Proc Natl Acad Sci U S A. 2015;112:E1587-93 pubmed publisher..We propose that homologous pairing and myosin VI-mediated transcriptional pause release account for the rapid and efficient expression of genes induced by an external stimulus. ..
- Rudnicki A, Isakov O, Ushakov K, Shivatzki S, Weiss I, Friedman L, et al. Next-generation sequencing of small RNAs from inner ear sensory epithelium identifies microRNAs and defines regulatory pathways. BMC Genomics. 2014;15:484 pubmed publisher..The results provide further support of the essential regulatory role of miRNAs in inner ear sensory epithelia and in regulating pathways that define development and growth of these cells. ..
- Kim Y, Wang S, Tymanskyj S, Ma L, Tao H, Zhang L. Dcc Mediates Functional Assembly of Peripheral Auditory Circuits. Sci Rep. 2016;6:23799 pubmed publisher..Our results suggest that Dcc plays an important role in the developmental formation of peripheral and central auditory circuits, and its mutation may contribute to sensorineural hearing loss. ..
- Mantela J, Jiang Z, Ylikoski J, Fritzsch B, Zacksenhaus E, Pirvola U. The retinoblastoma gene pathway regulates the postmitotic state of hair cells of the mouse inner ear. Development. 2005;132:2377-88 pubmed..Our findings demonstrate that the pRb pathway is required for hair cell quiescence and that manipulation of the cell cycle machinery disrupts the coordinated development within the inner ear sensory epithelia. ..
- Hoebe K, Du X, Goode J, Mann N, Beutler B. Lps2: a new locus required for responses to lipopolysaccharide, revealed by germline mutagenesis and phenotypic screening. J Endotoxin Res. 2003;9:250-5 pubmed..The Lps2 mutation does not preclude signaling initiated by peptidoglycan or unmethylated DNA. Hence, genetic data suggest that there is at least one 'missing' component of the LPS receptor complex that has yet to be found. ..
- 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. ..
- Hartman B, Nelson B, Reh T, Bermingham McDonogh O. Delta/notch-like EGF-related receptor (DNER) is expressed in hair cells and neurons in the developing and adult mouse inner ear. J Assoc Res Otolaryngol. 2010;11:187-201 pubmed publisher..We found no defects in expression of markers of supporting cells and glia or myelin, and no abnormalities in hair cells or neurons, suggesting that DNER plays a redundant role with other Notch ligands in cochlear development. ..
- Yu C, Lou J, Wu J, Pan L, Feng W, Zhang M. Membrane-induced lever arm expansion allows myosin VI to walk with large and variable step sizes. J Biol Chem. 2012;287:35021-35 pubmed publisher..This reversible, lipid membrane-dependent expansion of the LAE provides a mechanistic base for myosin VI to walk with large and variable step sizes. ..
- Schwander M, Sczaniecka A, Grillet N, Bailey J, Avenarius M, Najmabadi H, et al. A forward genetics screen in mice identifies recessive deafness traits and reveals that pejvakin is essential for outer hair cell function. J Neurosci. 2007;27:2163-75 pubmed
- Topsakal V, Hilgert N, van Dinther J, Tranebjaerg L, Rendtorff N, Zarowski A, et al. Genotype-phenotype correlation for DFNA22: characterization of non-syndromic, autosomal dominant, progressive sensorineural hearing loss due to MYO6 mutations. Audiol Neurootol. 2010;15:211-20 pubmed publisher..the phenotype of 2 Belgian families with SNHL linked to DFNA22, both with a pathogenic change in the deafness gene MYO6. The phenotypes of all hitherto reported DFNA22 families with mutations in the MYO6 gene have been studied and ..
- Sugimoto Y, Sato O, Watanabe S, Ikebe R, Ikebe M, Wakabayashi K. Reverse conformational changes of the light chain-binding domain of myosin V and VI processive motor heads during and after hydrolysis of ATP by small-angle X-ray solution scattering. J Mol Biol. 2009;392:420-35 pubmed publisher..The results suggest that some additional alterations or elements are required for MVI-S1 to take maximal working strokes along the actin filament. ..
- Giese A, Ezan J, Wang L, Lasvaux L, Lembo F, Mazzocco C, et al. Gipc1 has a dual role in Vangl2 trafficking and hair bundle integrity in the inner ear. Development. 2012;139:3775-85 pubmed