|
|
Proc Natl Acad Sci U S A. 1996 April 16; 93(8): 3232–3237. | PMCID: PMC39588 |
Human myosin VIIA responsible for the Usher 1B syndrome: a predicted membrane-associated motor protein expressed in developing sensory epithelia. D Weil, G Levy, I Sahly, F Levi-Acobas, S Blanchard, A El-Amraoui, F Crozet, H Philippe, M Abitbol, and C Petit Unite de Genetique Moleculaire Humaine, Centre National de la Recherche Scientifique Unite de Recherche Associee 1968, Institut Pasteur, Paris, France. Abstract The gene encoding human myosin VIIA is responsible for Usher syndrome type III (USH1B), a disease which associates profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. The reconstituted cDNA sequence presented here predicts a 2215 amino acid protein with a typical unconventional myosin structure. This protein is expected to dimerize into a two-headed molecule. The C terminus of its tail shares homology with the membrane-binding domain of the band 4.1 protein superfamily. The gene consists of 48 coding exons. It encodes several alternatively spliced forms. In situ hybridization analysis in human embryos demonstrates that the myosin VIIA gene is expressed in the pigment epithelium and the photoreceptor cells of the retina, thus indicating that both cell types may be involved in the USH1B retinal degenerative process. In addition, the gene is expressed in the human embryonic cochlear and vestibular neuroepithelia. We suggest that deafness and vestibular dysfunction in USH1B patients result from a defect in the morphogenesis of the inner ear sensory cell stereocilia. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.9M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References. Images in this article Click on the image to see a larger version. These references are in PubMed. This may not be the complete list of references from this article. - Kaplan J, Gerber S, Bonneau D, Rozet JM, Delrieu O, Briard ML, Dollfus H, Ghazi I, Dufier JL, Frézal J, et al. A gene for Usher syndrome type I (USH1A) maps to chromosome 14q. Genomics. 1992 Dec;14(4):979–987. [PubMed]
- Smith RJ, Berlin CI, Hejtmancik JF, Keats BJ, Kimberling WJ, Lewis RA, Möller CG, Pelias MZ, Tranebjaerg L. Clinical diagnosis of the Usher syndromes. Usher Syndrome Consortium. Am J Med Genet. 1994 Mar 1;50(1):32–38. [PubMed]
- Gibson F, Walsh J, Mburu P, Varela A, Brown KA, Antonio M, Beisel KW, Steel KP, Brown SD. A type VII myosin encoded by the mouse deafness gene shaker-1. Nature. 1995 Mar 2;374(6517):62–64. [PubMed]
- Steel KP, Bock GR. Hereditary inner-ear abnormalities in animals. Relationships with human abnormalities. Arch Otolaryngol. 1983 Jan;109(1):22–29. [PubMed]
- Abitbol M, Menini C, Delezoide AL, Rhyner T, Vekemans M, Mallet J. Nucleus basalis magnocellularis and hippocampus are the major sites of FMR-1 expression in the human fetal brain. Nat Genet. 1993 Jun;4(2):147–153. [PubMed]
- Kozak M. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res. 1984 Jan 25;12(2):857–872. [PubMed]
- Cheney RE, Riley MA, Mooseker MS. Phylogenetic analysis of the myosin superfamily. Cell Motil Cytoskeleton. 1993;24(4):215–223. [PubMed]
- Wolenski JS. Regulation of calmodulin-binding myosins. Trends Cell Biol. 1995 Aug;5(8):310–316. [PubMed]
- Rayment I, Rypniewski WR, Schmidt-Bäse K, Smith R, Tomchick DR, Benning MM, Winkelmann DA, Wesenberg G, Holden HM. Three-dimensional structure of myosin subfragment-1: a molecular motor. Science. 1993 Jul 2;261(5117):50–58. [PubMed]
- Rayment I, Holden HM, Whittaker M, Yohn CB, Lorenz M, Holmes KC, Milligan RA. Structure of the actin-myosin complex and its implications for muscle contraction. Science. 1993 Jul 2;261(5117):58–65. [PubMed]
- Hasson T, Mooseker MS. Porcine myosin-VI: characterization of a new mammalian unconventional myosin. J Cell Biol. 1994 Oct;127(2):425–440. [PubMed]
- Espreafico EM, Cheney RE, Matteoli M, Nascimento AA, De Camilli PV, Larson RE, Mooseker MS. Primary structure and cellular localization of chicken brain myosin-V (p190), an unconventional myosin with calmodulin light chains. J Cell Biol. 1992 Dec;119(6):1541–1557. [PubMed]
- Mercer JA, Seperack PK, Strobel MC, Copeland NG, Jenkins NA. Novel myosin heavy chain encoded by murine dilute coat colour locus. Nature. 1991 Feb 21;349(6311):709–713. [PubMed]
- Xie X, Harrison DH, Schlichting I, Sweet RM, Kalabokis VN, Szent-Györgyi AG, Cohen C. Structure of the regulatory domain of scallop myosin at 2.8 A resolution. Nature. 1994 Mar 24;368(6469):306–312. [PubMed]
- Houdusse A, Cohen C. Target sequence recognition by the calmodulin superfamily: implications from light chain binding to the regulatory domain of scallop myosin. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10644–10647. [PubMed]
- Lupas A, Van Dyke M, Stock J. Predicting coiled coils from protein sequences. Science. 1991 May 24;252(5010):1162–1164. [PubMed]
- Cheney RE, O'Shea MK, Heuser JE, Coelho MV, Wolenski JS, Espreafico EM, Forscher P, Larson RE, Mooseker MS. Brain myosin-V is a two-headed unconventional myosin with motor activity. Cell. 1993 Oct 8;75(1):13–23. [PubMed]
- Horowitz JA, Hammer JA., 3rd A new Acanthamoeba myosin heavy chain. Cloning of the gene and immunological identification of the polypeptide. J Biol Chem. 1990 Nov 25;265(33):20646–20652. [PubMed]
- Adams RJ, Pollard TD. Membrane-bound myosin-I provides new mechanisms in cell motility. Cell Motil Cytoskeleton. 1989;14(2):178–182. [PubMed]
- Hayden SM, Wolenski JS, Mooseker MS. Binding of brush border myosin I to phospholipid vesicles. J Cell Biol. 1990 Aug;111(2):443–451. [PubMed]
- Reizes O, Barylko B, Li C, Südhof TC, Albanesi JP. Domain structure of a mammalian myosin I beta. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6349–6353. [PubMed]
- Takeuchi K, Kawashima A, Nagafuchi A, Tsukita S. Structural diversity of band 4.1 superfamily members. J Cell Sci. 1994 Jul;107(Pt 7):1921–1928. [PubMed]
- Rees DJ, Ades SE, Singer SJ, Hynes RO. Sequence and domain structure of talin. Nature. 1990 Oct 18;347(6294):685–689. [PubMed]
- Tsukita S, Oishi K, Sato N, Sagara J, Kawai A, Tsukita S. ERM family members as molecular linkers between the cell surface glycoprotein CD44 and actin-based cytoskeletons. J Cell Biol. 1994 Jul;126(2):391–401. [PubMed]
- Smith CW, Patton JG, Nadal-Ginard B. Alternative splicing in the control of gene expression. Annu Rev Genet. 1989;23:527–577. [PubMed]
- Halsall DJ, Hammer JA., 3rd A second isoform of chicken brush border myosin I contains a 29-residue inserted sequence that binds calmodulin. FEBS Lett. 1990 Jul 2;267(1):126–130. [PubMed]
- Ruppert C, Kroschewski R, Bähler M. Identification, characterization and cloning of myr 1, a mammalian myosin-I. J Cell Biol. 1993 Mar;120(6):1393–1403. [PubMed]
- Kellerman KA, Miller KG. An unconventional myosin heavy chain gene from Drosophila melanogaster. J Cell Biol. 1992 Nov;119(4):823–834. [PubMed]
- George EL, Ober MB, Emerson CP., Jr Functional domains of the Drosophila melanogaster muscle myosin heavy-chain gene are encoded by alternatively spliced exons. Mol Cell Biol. 1989 Jul;9(7):2957–2974. [PubMed]
- Hudspeth AJ, Gillespie PG. Pulling springs to tune transduction: adaptation by hair cells. Neuron. 1994 Jan;12(1):1–9. [PubMed]
- Ashmore JF, Kolston PJ. Hair cell based amplification in the cochlea. Curr Opin Neurobiol. 1994 Aug;4(4):503–508. [PubMed]
- Mullen RJ, LaVail MM. Inherited retinal dystrophy: primary defect in pigment epithelium determined with experimental rat chimeras. Science. 1976 May 21;192(4241):799–801. [PubMed]
- Hasson T, Heintzelman MB, Santos-Sacchi J, Corey DP, Mooseker MS. Expression in cochlea and retina of myosin VIIa, the gene product defective in Usher syndrome type 1B. Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9815–9819. [PubMed]
|
This article has been 
