Myosin VIIA, important for human auditory function, is necessary for Drosophila auditory organ development.

Myosin VIIA, important for human auditory function, is necessary for Drosophila auditory organ development.
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DOI:
10.1371/journal.pone.0002115
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发表时间:
2008-05-07
期刊:
影响因子:
3.7
通讯作者:
Eberl, Daniel F.
Eberl, Daniel F.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Todi, Sokol V.;Sivan-Loukianova, Elena;Jacobs, Julie S.;Kiehart, Daniel P.;Eberl, Daniel F.

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肌球蛋白VIIA(MyoVIIA)是脊椎动物听力所需的一种非常规肌球蛋白。人类的听觉传导发生在感觉毛细胞中,其顶端突起呈阶梯状排列,称为静纤毛。在这些毛细胞中,MyoVIIA维持静纤毛组织。果蝇MyoVIIA直向同源物crinkled(ck)中的严重突变是半致死性的,并且通过破坏触角听觉器官(约翰斯顿器官,JO)组织而导致耳聋。ck/MyoVIIA突变导致听觉传导单位(视皮层)从角质层的顶端脱离,所述角质层将触角振动作为机械刺激传递到JO。使用果蝇表达GFP标记的NompA,在果蝇的听觉器官组织所需的蛋白质,我们研究了通过共聚焦显微镜和细胞外电生理的作用,CK/MyoVIIA在JO的发展和维护。在这里,我们表明,CK/MyoVIIA是必要的早期发育天线的初始顶端附件的关节关节的关节。ck/MyoVIIA也是在整个成年期维持视神经附着所必需的。此外,在成人JO中,ck/MyoVIIA与非肌肉肌球蛋白II发生遗传相互作用(通过其调节轻链蛋白和肌球蛋白II磷酸酶的肌球蛋白结合亚基)。这种遗传相互作用以前没有观察到在Escheropidia。因此,这些因子是调节脊椎动物中MyoVIIA活性的候选因子。我们的研究结果表明,MyoVIIA在无脊椎动物和脊椎动物的听觉器官发育和维持中起着进化上保守的作用,增强了我们对听觉器官发育和功能的理解,并为未来的研究提供了重要线索。
Myosin VIIA (MyoVIIA) is an unconventional myosin necessary for vertebrate audition. Human auditory transduction occurs in sensory hair cells with a staircase-like arrangement of apical protrusions called stereocilia. In these hair cells, MyoVIIA maintains stereocilia organization. Severe mutations in the Drosophila MyoVIIA orthologue, crinkled (ck), are semi-lethal and lead to deafness by disrupting antennal auditory organ (Johnston's Organ, JO) organization. ck/MyoVIIA mutations result in apical detachment of auditory transduction units (scolopidia) from the cuticle that transmits antennal vibrations as mechanical stimuli to JO. Using flies expressing GFP-tagged NompA, a protein required for auditory organ organization in Drosophila, we examined the role of ck/MyoVIIA in JO development and maintenance through confocal microscopy and extracellular electrophysiology. Here we show that ck/MyoVIIA is necessary early in the developing antenna for initial apical attachment of the scolopidia to the articulating joint. ck/MyoVIIA is also necessary to maintain scolopidial attachment throughout adulthood. Moreover, in the adult JO, ck/MyoVIIA genetically interacts with the non-muscle myosin II (through its regulatory light chain protein and the myosin binding subunit of myosin II phosphatase). Such genetic interactions have not previously been observed in scolopidia. These factors are therefore candidates for modulating MyoVIIA activity in vertebrates. Our findings indicate that MyoVIIA plays evolutionarily conserved roles in auditory organ development and maintenance in invertebrates and vertebrates, enhancing our understanding of auditory organ development and function, as well as providing significant clues for future research.
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