The deaf mouse mutant whirler suggests a role for whirlin in actin filament dynamics and stereocilia development.
The deaf mouse mutant whirler suggests a role for whirlin in actin filament dynamics and stereocilia development.
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DOI：
10.1002/cm.20199
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发表时间：
2007-07
影响因子：
--
通讯作者：
Steel, Karen P
中科院分区：
文献类型：
--
作者：
Mogensen, Mette M;Rzadzinska, Agnieszka;Steel, Karen P
立体纤毛是指状突起，在耳蜗感觉毛细胞的顶端表面形成毛束，负责机械感觉并最终感知声音。立体纤毛的肌动蛋白细胞骨架包含数百个紧密交联的平行肌动蛋白丝，呈准晶排列，对其功能至关重要。虽然已经确定了几个与纤毛发育相关的基因，但负责纤毛生长、维持和毛束组织的分子机制尚未完全解决。在这里，我们提供进一步表征的立体纤毛的小鼠突变体。我们发现，在whirler突变体中，旋转蛋白的缺乏导致了短的、直径更大的立体纤毛，而内毛细胞中肌动蛋白丝的数量却没有相应的增加。然而，在旋转突变体中，肌动蛋白丝堆积密度明显下降。旋流突变体的每条立体纤毛顶端的电子密度明显呈斑块状和不规则状，而对照组的电子密度呈均匀带状。旋型纯合子外毛细胞立体纤毛直径增加，束内高度变化。外毛细胞立纤毛数量显著减少，立纤毛之间的中心间距比野生型大。我们的研究结果表明，在出生后立体纤毛伸长过程中，旋转蛋白在肌动蛋白丝的堆积和动力学中起重要作用。
Stereocilia, finger-like projections forming the hair bundle on the apical surface of sensory hair cells in the cochlea, are responsible for mechanosensation and ultimately the perception of sound. The actin cytoskeleton of the stereocilia contains hundreds of tightly cross-linked parallel actin filaments in a paracrystalline array and it is vital for their function. Although several genes have been identified and associated with stereocilia development, the molecular mechanisms responsible for stereocilia growth, maintenance and organisation of the hair bundle have not been fully resolved. Here we provide further characterisation of the stereocilia of the whirler mouse mutant. We found that a lack of whirlin protein in whirler mutants results in short stereocilia with larger diameters without a corresponding increase in the number of actin filaments in inner hair cells. However, a decrease in the actin filament packing density was evident in the whirler mutant. The electron-density at the tip of each stereocilium was markedly patchy and irregular in the whirler mutants compared with a uniform band in controls. The outer hair cell stereocilia of the whirler homozygote also showed an increase in diameter and variable heights within bundles. The number of outer hair cell stereocilia was significantly reduced and the centre-to-centre spacing between the stereocilia was greater than in the wildtype. Our findings suggest that whirlin plays an important role in actin filament packing and dynamics during postnatal stereocilium elongation.