Myosin VIIA is protein that in humans is encoded by the MYO7Agene.[1] Myosin VIIA is a member of the unconventional myosin superfamily of proteins.[2] Myosins are actin binding molecular motors that use the enzymatic conversion of ATP - ADP + inorganic phosphate (Pi) to provide the energy for movement.
Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. Myosin VIIA is an unconventional myosin with a very short tail. Unconventional myosins have diverse functions in eukaryotic cells and are primarily thought to be involved in the movement or linkage of intra-cellular membranes and organelles to the actin cytoskeleton via interactions mediated by their highly divergent tail domains.
Mutations in the MYO7A gene cause the Usher syndrome type 1B, a combined deafness/blindness disorder.[2] Affected individuals are typically profoundly deaf at birth and then undergo progressive retinal degeneration.[3]
Model organisms have been used in the study of MYO7A function. A spontaneous mutant mouse line, called Myo7ash1-6J[15] was generated. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[13][16] Twenty three tests were carried out on mutant mice and ten significant abnormalities were observed.[13] Male homozygousmutant mice displayed a decreased body weight, a decrease in body fat, improved glucose tolerance and abnormal pelvic girdle bone morphology. Homozygous mutant mice of both sex displayed various abnormalities in a modified SHIRPA test, including abnormal gait, tail dragging and an absence of pinnareflex, a decrease in grip strength, an increased thermal pain threshold, severe hearing impairment and a number of abnormal indirect calorimetry and clinical chemistry parameters.[13]
References
↑Hasson T, Skowron JF, Gilbert DJ, Avraham KB, Perry WL, Bement WM, Anderson BL, Sherr EH, Chen ZY, Greene LA, Ward DC, Corey DP, Mooseker MS, Copeland NG, Jenkins NA (Sep 1996). "Mapping of unconventional myosins in mouse and human". Genomics. 36 (3): 431–9. doi:10.1006/geno.1996.0488. PMID8884266.
↑ 2.02.1Weil D, Blanchard S, Kaplan J, Guilford P, Gibson F, Walsh J, Mburu P, Varela A, Levilliers J, Weston MD (Mar 1995). "Defective myosin VIIA gene responsible for Usher syndrome type 1B". Nature. 374 (6517): 60–1. doi:10.1038/374060a0. PMID7870171.
↑Smith RJ, Berlin CI, Hejtmancik JF, Keats BJ, Kimberling WJ, Lewis RA, Möller CG, Pelias MZ, Tranebjaerg L (Mar 1994). "Clinical diagnosis of the Usher syndromes. Usher Syndrome Consortium". American Journal of Medical Genetics. 50 (1): 32–8. doi:10.1002/ajmg.1320500107. PMID8160750.
Wolfrum U (2004). "The cellular function of the usher gene product myosin VIIa is specified by its ligands". Advances in Experimental Medicine and Biology. 533: 133–42. doi:10.1007/978-1-4615-0067-4_17. PMID15180257.
Kimberling WJ, Möller CG, Davenport S, Priluck IA, Beighton PH, Greenberg J, Reardon W, Weston MD, Kenyon JB, Grunkemeyer JA (Dec 1992). "Linkage of Usher syndrome type I gene (USH1B) to the long arm of chromosome 11". Genomics. 14 (4): 988–94. doi:10.1016/S0888-7543(05)80121-1. PMID1478677.
Guilford P, Ayadi H, Blanchard S, Chaib H, Le Paslier D, Weissenbach J, Drira M, Petit C (Jun 1994). "A human gene responsible for neurosensory, non-syndromic recessive deafness is a candidate homologue of the mouse sh-1 gene". Human Molecular Genetics. 3 (6): 989–93. doi:10.1093/hmg/3.6.989. PMID7951250.
Wagenaar M, ter Rahe B, van Aarem A, Huygen P, Admiraal R, Bleeker-Wagemakers E, Pinckers A, Kimberling W, Cremers C (Nov 1995). "Clinical findings in obligate carriers of type I Usher syndrome". American Journal of Medical Genetics. 59 (3): 375–9. doi:10.1002/ajmg.1320590319. PMID8599365.
Tamagawa Y, Kitamura K, Ishida T, Ishikawa K, Tanaka H, Tsuji S, Nishizawa M (Jun 1996). "A gene for a dominant form of non-syndromic sensorineural deafness (DFNA11) maps within the region containing the DFNB2 recessive deafness gene". Human Molecular Genetics. 5 (6): 849–52. doi:10.1093/hmg/5.6.849. PMID8776602.
Chen ZY, Hasson T, Kelley PM, Schwender BJ, Schwartz MF, Ramakrishnan M, Kimberling WJ, Mooseker MS, Corey DP (Sep 1996). "Molecular cloning and domain structure of human myosin-VIIa, the gene product defective in Usher syndrome 1B". Genomics. 36 (3): 440–8. doi:10.1006/geno.1996.0489. PMID8884267.
Lévy G, Levi-Acobas F, Blanchard S, Gerber S, Larget-Piet D, Chenal V, Liu XZ, Newton V, Steel KP, Brown SD, Munnich A, Kaplan J, Petit C, Weil D (Jan 1997). "Myosin VIIA gene: heterogeneity of the mutations responsible for Usher syndrome type IB". Human Molecular Genetics. 6 (1): 111–6. doi:10.1093/hmg/6.1.111. PMID9002678.
Kelley PM, Weston MD, Chen ZY, Orten DJ, Hasson T, Overbeck LD, Pinnt J, Talmadge CB, Ing P, Mooseker MS, Corey D, Sumegi J, Kimberling WJ (Feb 1997). "The genomic structure of the gene defective in Usher syndrome type Ib (MYO7A)". Genomics. 40 (1): 73–9. doi:10.1006/geno.1996.4545. PMID9070921.
Liu XZ, Walsh J, Mburu P, Kendrick-Jones J, Cope MJ, Steel KP, Brown SD (Jun 1997). "Mutations in the myosin VIIA gene cause non-syndromic recessive deafness". Nature Genetics. 16 (2): 188–90. doi:10.1038/ng0697-188. PMID9171832.
Weil D, Küssel P, Blanchard S, Lévy G, Levi-Acobas F, Drira M, Ayadi H, Petit C (Jun 1997). "The autosomal recessive isolated deafness, DFNB2, and the Usher 1B syndrome are allelic defects of the myosin-VIIA gene". Nature Genetics. 16 (2): 191–3. doi:10.1038/ng0697-191. PMID9171833.
Liu XZ, Walsh J, Tamagawa Y, Kitamura K, Nishizawa M, Steel KP, Brown SD (Nov 1997). "Autosomal dominant non-syndromic deafness caused by a mutation in the myosin VIIA gene". Nature Genetics. 17 (3): 268–9. doi:10.1038/ng1197-268. PMID9354784.