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. 1998 Apr;148(4):1963–1972. doi: 10.1093/genetics/148.4.1963

Molecular genetic dissection of mouse unconventional myosin-VA: tail region mutations.

J D Huang 1, V Mermall 1, M C Strobel 1, L B Russell 1, M S Mooseker 1, N G Copeland 1, N A Jenkins 1
PMCID: PMC1460104  PMID: 9560409

Abstract

We used an RT-PCR-based sequencing approach to identify the mutations responsible for 17 viable dilute alleles, a mouse-coat-color locus encoding unconventional myosin-VA. Ten of the mutations mapped to the MyoVA tail and are reported here. These mutations represent the first extensive collection of tail mutations reported for any unconventional mammalian myosin. They identify sequences important for tail function and identify domains potentially involved in cargo binding and/or proper folding of the MyoVA tail. Our results also provide support for the notion that different myosin tail isoforms produced by alternative splicing encode important cell-type-specific functions.

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Selected References

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  1. Barbosa M. D., Nguyen Q. A., Tchernev V. T., Ashley J. A., Detter J. C., Blaydes S. M., Brandt S. J., Chotai D., Hodgman C., Solari R. C. Identification of the homologous beige and Chediak-Higashi syndrome genes. Nature. 1996 Jul 18;382(6588):262–265. doi: 10.1038/382262a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bedell M. A., Largaespada D. A., Jenkins N. A., Copeland N. G. Mouse models of human disease. Part II: recent progress and future directions. Genes Dev. 1997 Jan 1;11(1):11–43. doi: 10.1101/gad.11.1.11. [DOI] [PubMed] [Google Scholar]
  3. Cheney R. E., O'Shea M. K., Heuser J. E., Coelho M. V., Wolenski J. S., Espreafico E. M., Forscher P., Larson R. E., Mooseker M. S. Brain myosin-V is a two-headed unconventional myosin with motor activity. Cell. 1993 Oct 8;75(1):13–23. doi: 10.1016/S0092-8674(05)80080-7. [DOI] [PubMed] [Google Scholar]
  4. Cooper T. A. In vitro splicing of cardiac troponin T precursors. Exon mutations disrupt splicing of the upstream intron. J Biol Chem. 1992 Mar 15;267(8):5330–5338. [PubMed] [Google Scholar]
  5. Cooper T. A., Ordahl C. P. Nucleotide substitutions within the cardiac troponin T alternative exon disrupt pre-mRNA alternative splicing. Nucleic Acids Res. 1989 Oct 11;17(19):7905–7921. doi: 10.1093/nar/17.19.7905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dekker-Ohno K., Hayasaka S., Takagishi Y., Oda S., Wakasugi N., Mikoshiba K., Inouye M., Yamamura H. Endoplasmic reticulum is missing in dendritic spines of Purkinje cells of the ataxic mutant rat. Brain Res. 1996 Apr 1;714(1-2):226–230. doi: 10.1016/0006-8993(95)01560-4. [DOI] [PubMed] [Google Scholar]
  7. Engle L. J., Kennett R. H. Cloning, analysis, and chromosomal localization of myoxin (MYH12), the human homologue to the mouse dilute gene. Genomics. 1994 Feb;19(3):407–416. doi: 10.1006/geno.1994.1088. [DOI] [PubMed] [Google Scholar]
  8. Espreafico E. M., Cheney R. E., Matteoli M., Nascimento A. A., De Camilli P. V., Larson R. E., Mooseker M. S. 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. doi: 10.1083/jcb.119.6.1541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fu X. D., Katz R. A., Skalka A. M., Maniatis T. The role of branchpoint and 3'-exon sequences in the control of balanced splicing of avian retrovirus RNA. Genes Dev. 1991 Feb;5(2):211–220. doi: 10.1101/gad.5.2.211. [DOI] [PubMed] [Google Scholar]
  10. Gibson F., Walsh J., Mburu P., Varela A., Brown K. A., Antonio M., Beisel K. W., Steel K. P., Brown S. D. A type VII myosin encoded by the mouse deafness gene shaker-1. Nature. 1995 Mar 2;374(6517):62–64. doi: 10.1038/374062a0. [DOI] [PubMed] [Google Scholar]
  11. Haarer B. K., Petzold A., Lillie S. H., Brown S. S. Identification of MYO4, a second class V myosin gene in yeast. J Cell Sci. 1994 Apr;107(Pt 4):1055–1064. doi: 10.1242/jcs.107.4.1055. [DOI] [PubMed] [Google Scholar]
  12. Hall D. H., Hedgecock E. M. Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans. Cell. 1991 May 31;65(5):837–847. doi: 10.1016/0092-8674(91)90391-b. [DOI] [PubMed] [Google Scholar]
  13. Hampson R. K., La Follette L., Rottman F. M. Alternative processing of bovine growth hormone mRNA is influenced by downstream exon sequences. Mol Cell Biol. 1989 Apr;9(4):1604–1610. doi: 10.1128/mcb.9.4.1604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Haraldsson A., Weemaes C. M., Bakkeren J. A., Happle R. Griscelli disease with cerebral involvement. Eur J Pediatr. 1991 Apr;150(6):419–422. doi: 10.1007/BF02093723. [DOI] [PubMed] [Google Scholar]
  15. Hasson T., Mooseker M. S. Vertebrate unconventional myosins. J Biol Chem. 1996 Jul 12;271(28):16431–16434. doi: 10.1074/jbc.271.28.16431. [DOI] [PubMed] [Google Scholar]
  16. 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. Mapping of unconventional myosins in mouse and human. Genomics. 1996 Sep 15;36(3):431–439. doi: 10.1006/geno.1996.0488. [DOI] [PubMed] [Google Scholar]
  17. Helfman D. M., Ricci W. M., Finn L. A. Alternative splicing of tropomyosin pre-mRNAs in vitro and in vivo. Genes Dev. 1988 Dec;2(12A):1627–1638. doi: 10.1101/gad.2.12a.1627. [DOI] [PubMed] [Google Scholar]
  18. Huang J. D., Cope M. J., Mermall V., Strobel M. C., Kendrick-Jones J., Russell L. B., Mooseker M. S., Copeland N. G., Jenkins N. A. Molecular genetic dissection of mouse unconventional myosin-VA: head region mutations. Genetics. 1998 Apr;148(4):1951–1961. doi: 10.1093/genetics/148.4.1951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hurvitz H., Gillis R., Klaus S., Klar A., Gross-Kieselstein F., Okon E. A kindred with Griscelli disease: spectrum of neurological involvement. Eur J Pediatr. 1993 May;152(5):402–405. doi: 10.1007/BF01955897. [DOI] [PubMed] [Google Scholar]
  20. Jansen R. P., Dowzer C., Michaelis C., Galova M., Nasmyth K. Mother cell-specific HO expression in budding yeast depends on the unconventional myosin myo4p and other cytoplasmic proteins. Cell. 1996 Mar 8;84(5):687–697. doi: 10.1016/s0092-8674(00)81047-8. [DOI] [PubMed] [Google Scholar]
  21. Johnston G. C., Prendergast J. A., Singer R. A. The Saccharomyces cerevisiae MYO2 gene encodes an essential myosin for vectorial transport of vesicles. J Cell Biol. 1991 May;113(3):539–551. doi: 10.1083/jcb.113.3.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Katz R. A., Skalka A. M. Control of retroviral RNA splicing through maintenance of suboptimal processing signals. Mol Cell Biol. 1990 Feb;10(2):696–704. doi: 10.1128/mcb.10.2.696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lillie S. H., Brown S. S. Immunofluorescence localization of the unconventional myosin, Myo2p, and the putative kinesin-related protein, Smy1p, to the same regions of polarized growth in Saccharomyces cerevisiae. J Cell Biol. 1994 May;125(4):825–842. doi: 10.1083/jcb.125.4.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Liu X. Z., Walsh J., Mburu P., Kendrick-Jones J., Cope M. J., Steel K. P., Brown S. D. Mutations in the myosin VIIA gene cause non-syndromic recessive deafness. Nat Genet. 1997 Jun;16(2):188–190. doi: 10.1038/ng0697-188. [DOI] [PubMed] [Google Scholar]
  25. Mardon H. J., Sebastio G., Baralle F. E. A role for exon sequences in alternative splicing of the human fibronectin gene. Nucleic Acids Res. 1987 Oct 12;15(19):7725–7733. doi: 10.1093/nar/15.19.7725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Marker P. C., Seung K., Bland A. E., Russell L. B., Kingsley D. M. Spectrum of Bmp5 mutations from germline mutagenesis experiments in mice. Genetics. 1997 Feb;145(2):435–443. doi: 10.1093/genetics/145.2.435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mercer J. A., Seperack P. K., Strobel M. C., Copeland N. G., Jenkins N. A. Novel myosin heavy chain encoded by murine dilute coat colour locus. Nature. 1991 Feb 21;349(6311):709–713. doi: 10.1038/349709a0. [DOI] [PubMed] [Google Scholar]
  28. Miyamoto H., Nihonmatsu I., Kondo S., Ueda R., Togashi S., Hirata K., Ikegami Y., Yamamoto D. canoe encodes a novel protein containing a GLGF/DHR motif and functions with Notch and scabrous in common developmental pathways in Drosophila. Genes Dev. 1995 Mar 1;9(5):612–625. doi: 10.1101/gad.9.5.612. [DOI] [PubMed] [Google Scholar]
  29. Moore K. J., Testa J. R., Francke U., Milatovich A., Copeland N. G., Jenkins N. A. Cloning and regional assignment of the human myosin heavy chain 12 (MYH12) gene to chromosome band 15q21. Cytogenet Cell Genet. 1995;69(1-2):53–58. doi: 10.1159/000133937. [DOI] [PubMed] [Google Scholar]
  30. Nagle D. L., Karim M. A., Woolf E. A., Holmgren L., Bork P., Misumi D. J., McGrail S. H., Dussault B. J., Jr, Perou C. M., Boissy R. E. Identification and mutation analysis of the complete gene for Chediak-Higashi syndrome. Nat Genet. 1996 Nov;14(3):307–311. doi: 10.1038/ng1196-307. [DOI] [PubMed] [Google Scholar]
  31. Pastural E., Barrat F. J., Dufourcq-Lagelouse R., Certain S., Sanal O., Jabado N., Seger R., Griscelli C., Fischer A., de Saint Basile G. Griscelli disease maps to chromosome 15q21 and is associated with mutations in the myosin-Va gene. Nat Genet. 1997 Jul;16(3):289–292. doi: 10.1038/ng0797-289. [DOI] [PubMed] [Google Scholar]
  32. Penotti F. E. Human pre-mRNA splicing signals. J Theor Biol. 1991 Jun 7;150(3):385–420. doi: 10.1016/s0022-5193(05)80436-9. [DOI] [PubMed] [Google Scholar]
  33. Prasad R., Gu Y., Alder H., Nakamura T., Canaani O., Saito H., Huebner K., Gale R. P., Nowell P. C., Kuriyama K. Cloning of the ALL-1 fusion partner, the AF-6 gene, involved in acute myeloid leukemias with the t(6;11) chromosome translocation. Cancer Res. 1993 Dec 1;53(23):5624–5628. [PubMed] [Google Scholar]
  34. Russell W. L., Hunsicker P. R., Raymer G. D., Steele M. H., Stelzner K. F., Thompson H. M. Dose--response curve for ethylnitrosourea-induced specific-locus mutations in mouse spermatogonia. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3589–3591. doi: 10.1073/pnas.79.11.3589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sanders G., Lichte B., Meyer H. E., Kilimann M. W. cDNA encoding the chicken ortholog of the mouse dilute gene product. Sequence comparison reveals a myosin I subfamily with conserved C-terminal domains. FEBS Lett. 1992 Oct 26;311(3):295–298. doi: 10.1016/0014-5793(92)81123-4. [DOI] [PubMed] [Google Scholar]
  36. Seperack P. K., Mercer J. A., Strobel M. C., Copeland N. G., Jenkins N. A. Retroviral sequences located within an intron of the dilute gene alter dilute expression in a tissue-specific manner. EMBO J. 1995 May 15;14(10):2326–2332. doi: 10.1002/j.1460-2075.1995.tb07227.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Steingrimsdottir H., Rowley G., Dorado G., Cole J., Lehmann A. R. Mutations which alter splicing in the human hypoxanthine-guanine phosphoribosyltransferase gene. Nucleic Acids Res. 1992 Mar 25;20(6):1201–1208. doi: 10.1093/nar/20.6.1201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Takagishi Y., Oda S., Hayasaka S., Dekker-Ohno K., Shikata T., Inouye M., Yamamura H. The dilute-lethal (dl) gene attacks a Ca2+ store in the dendritic spine of Purkinje cells in mice. Neurosci Lett. 1996 Sep 13;215(3):169–172. doi: 10.1016/0304-3940(96)12967-0. [DOI] [PubMed] [Google Scholar]
  39. Watakabe A., Tanaka K., Shimura Y. The role of exon sequences in splice site selection. Genes Dev. 1993 Mar;7(3):407–418. doi: 10.1101/gad.7.3.407. [DOI] [PubMed] [Google Scholar]
  40. Weil D., Blanchard S., Kaplan J., Guilford P., Gibson F., Walsh J., Mburu P., Varela A., Levilliers J., Weston M. D. Defective myosin VIIA gene responsible for Usher syndrome type 1B. Nature. 1995 Mar 2;374(6517):60–61. doi: 10.1038/374060a0. [DOI] [PubMed] [Google Scholar]
  41. Weston M. D., Kelley P. M., Overbeck L. D., Wagenaar M., Orten D. J., Hasson T., Chen Z. Y., Corey D., Mooseker M., Sumegi J. Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients. Am J Hum Genet. 1996 Nov;59(5):1074–1083. [PMC free article] [PubMed] [Google Scholar]
  42. Wu X., Bowers B., Wei Q., Kocher B., Hammer J. A., 3rd Myosin V associates with melanosomes in mouse melanocytes: evidence that myosin V is an organelle motor. J Cell Sci. 1997 Apr;110(Pt 7):847–859. doi: 10.1242/jcs.110.7.847. [DOI] [PubMed] [Google Scholar]
  43. Zhao L. P., Koslovsky J. S., Reinhard J., Bähler M., Witt A. E., Provance D. W., Jr, Mercer J. A. Cloning and characterization of myr 6, an unconventional myosin of the dilute/myosin-V family. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10826–10831. doi: 10.1073/pnas.93.20.10826. [DOI] [PMC free article] [PubMed] [Google Scholar]

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