Myosin VIIA defects, which underlie the Usher 1B syndrome in humans, lead to deafness in Drosophila.
In vertebrates, auditory and vestibular transduction occurs on apical projections (stereocilia) of specialized cells (hair cells). Mutations in myosin VIIA (myoVIIA), an unconventional myosin, lead to deafness and balance anomalies in humans, mice, and zebrafish; individuals are deaf, and stereocilia are disorganized. The exact mechanism through which myoVIIA mutations result in these inner-ear anomalies is unknown. Proposed inner-ear functions for myoVIIA include anchoring transduction channels to the stereocilia membrane, trafficking stereocilia linking components, and anchoring hair cells by associating with adherens junctions. The Drosophila myoVIIA homolog is crinkled (ck). The Drosophila auditory organ, Johnston's organ (JO), is developmentally and functionally related to the vertebrate inner ear. Both derive from modified epithelial cells specified by atonal and spalt homolog expression, and both transduce acoustic mechanical energy (and references therein). Here, we show that loss of ck/myoVIIA function leads to complete deafness in Drosophila by disrupting the integrity of the scolopidia that transduce auditory signals. We demonstrate that ck/myoVIIA functions to organize the auditory organ, that it is functionally required in neuronal and support cells, that it is not required for TRPV channel localization, and that it is not essential for scolopidial-cell-junction integrity.
Todi
Sokol V
SV
Neuroscience Graduate Program, Department of Biological Sciences, The University of Iowa, Iowa City, Iowa 52242, USA.
Franke
Josef D
JD
Kiehart
Daniel P
DP
Eberl
Daniel F
DF
D000818:Animals; D003001:Cloning, Molecular; D003638:Deafness / Q000235:genetics*; D004330:Drosophila / Q000235:genetics* / Q000502:physiology; D004398:Dyneins / Q000235:genetics*; D007758:Ear, Inner / Q000378:metabolism*; D004594:Electrophysiology; D005072:Evoked Potentials, Auditory / Q000502:physiology*; D006198:Hair Cells, Auditory / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007365:Intercellular Junctions / Q000502:physiology; D018613:Microscopy, Confocal; D009154:Mutation / Q000235:genetics; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*
C000631455:MYO7A protein, human; C000631456:Myo7a protein, mouse; D000081412:Myosin VIIa; C000631458:myosin 7a, Drosophila; D009218:Myosins; D004398:Dyneins