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suggest a mechanism for Sisyphus (the Drosophila myosin XV homolog) in which it maintains a balance between actin and microtubule cytoskeleton components
Myosin 15 (show MYH15 Antibodies) isoforms can navigate between functionally distinct classes of stereocilia, and are independently required to assemble and then maintain the intricate hair bundle architecture.
myo15-subfragment 1 is a barbed-end-directed motor that moves actin filaments in a gliding assay using a power stroke of 7.9 nm. Myo15-S1 was rate limited by transit through strongly actin-bound states, similar to other processive myosin motors.
It was concluded that MyoXVa, whirlin, and Eps8 are integral components of the stereocilia tip complex, where Eps8 is a central actin-regulatory element for elongation of the stereocilia actin core.
endogenous myosin XVa localizes to the tips of the stereocilia of the cochlear and vestibular hair cells
myosin-XVa is a motor protein (show MYO7A Antibodies) that, in vivo, interacts with the third PDZ domain (show INADL Antibodies) of whirlin (show DFNB31 Antibodies) through its carboxy-terminal PDZ (show INADL Antibodies)-ligand. Myosin-XVa then delivers whirlin (show DFNB31 Antibodies) to the tips of stereocilia.
This comparison revealed that the absence of functional myosin-XVa does not disrupt adaptation of the mechanotransduction current during sustained bundle deflection.
The morphology of cochlear hair cell stereocilia in double mutants reflects a dominance of the more severe Myo15 (sh2/sh2) phenotype over the Whrn (wi/wi (show DFNB31 Antibodies)) phenotype.
The Ca(2 (show CA2 Antibodies)+) sensitivity of the mechanotransduction channels and the fast adaptation require a structural environment that is dependent on myosin-XVa and is disrupted in Myo15(sh2/sh2) inner hair cells, but not in Myo15(sh2/sh2) outer hair cells.
Six novel MYO15 mutations were identified in a family with nonsyndromic hearing loss.
MYO15A mutation was corrected by CRISPR/Cas9 system in the iPSCs and rescued the morphology and function of the derived hair cell-like cells.
Study reports 14 novel recessive mutations in MYO15A that might be a deafness-causing mutations. Also, in the inner ear, myosin 15 (show MYH15 Antibodies) seems to be necessary both for the development and the long-term maintenance of stereocilia.
We identified in Moroccan deaf patients two mutations in PJVK (show DFNB59 Antibodies) and one mutation in MYO15A described for the first time in association with non-syndromic recessive hearing loss.
The MYO15A variant is a common cause of hearing loss in a northeastern Brazilian town.
Reconstruction of haplotype structure at MYO15A surrounding genomic regions indicated that the founder haplotype branched out in the past two to three centuries from a haplotype present worldwide. The MYO15A duplication emerges as the major cause of genetic hearing loss in Oman.
novel homozygous donor splice site mutation, c.4596 + 1G > A (IVS12 + 1G > A) was found in MYO15A gene
There are more than 39 deafness genes reported to cause non-syndromic hereditary hearing loss (HHL) in Iran, of which the most prevalent causative genes include GJB2, SLC26A4, MYO15A, and MYO7A. In addition, we highlight some of the more common genetic causes of syndromic HHL in Iran. [review]
Mutations in exon 2 of MYO15A may cause a less severe phenotype, facilitating the rapid identification of mutations in exon 2 among the 66 exons when linkage of less severe hearing loss to DFNB3 is detected
MYO15A mutations that affect domains other than the N-terminal domain, lead to profound sensorineural hearing loss throughout all frequencies.
Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments (By similarity). Required for the arrangement of stereocilia in mature hair bundles.
, myosin 10A
, myosin XV
, unconventional myosin class XV
, myosin XVA
, myosin xv
, shaker 2
, unconventional myosin-15
, unconventional myosin-XV