Myosin XVa localizes to the tips of inner ear sensory cell stereocilia and is essential for staircase formation of the hair bundle
Myosin XVa localizes to the tips of inner ear sensory cell stereocilia and is essential for staircase formation of the hair bundle
复制标题
DOI：
10.1073/pnas.2334417100
复制
发表时间：
2003-11-25
影响因子：
11.1
通讯作者：
Friedman, TB
中科院分区：
文献类型：
--
作者：
Belyantseva, IA;Boger, ET;Friedman, TB
编码非传统肌球蛋白XVA的基因突变与人类(DFNB3)和Shaker(Myo15(Sh2))小鼠的感觉神经性耳聋有关。在失聪的Myo15(Sh2/Sh2)小鼠，静毛纤毛较短，长度几乎相等，缺乏肌球蛋白XVA免疫反应。我们先前报道，肌球蛋白XVA的mRNA和蛋白在耳蜗毛细胞中表达。我们现在证明，在小鼠、大鼠和豚鼠身上，内源性肌球蛋白XVA定位于耳蜗毛细胞和前庭毛细胞的纤毛末端。肌球蛋白XVA定位与肌动蛋白细丝的带刺末端重叠，并延伸到立体纤毛的顶端质膜。基因枪介导的小鼠内耳感觉上皮细胞外植体的转基因显示肌球蛋白XVA-GFP选择性地聚集在体毛纤毛顶端，证实了天然肌球蛋白XVA的定位。在COS7细胞中的表达也表明肌球蛋白XVA-GFP靶向于丝状伪足顶端的动态肌动蛋白区域。在野生型小鼠中，在听觉和前庭毛细胞发育过程中，当毛束开始形成其特有的阶梯图案时，肌球蛋白XVA出现在立体纤毛的顶端。我们认为，肌球蛋白XVA对于立体纤毛在功能成熟过程中的渐进性延长是必不可少的。
Mutations of the gene encoding unconventional myosin XVa are associated with sensorineural deafness in humans (DFNB3) and shaker (Myo15(sh2)) mice. in deaf Myo15(sh2/sh2) mice, stereocilia are short, nearly equal in length, and lack myosin XVa immunoreactivity. We previously reported that myosin XVa mRNA and protein are expressed in cochlear hair cells. We now show that in the mouse, rat, and guinea pig, endogenous myosin XVa localizes to the tips of the stereocilia of the cochlear and vestibular hair cells. Myosin XVa localization overlaps with the barbed ends of actin filaments and extends to the apical plasma membrane of the stereocilia. Gene gun-mediated transfection of mouse inner ear sensory epithelia explants shows selective accumulation of myosin XVa-GFP at the tips of stereocilia, confirming the localization of native myosin XVa. Expression in COS7 cells also reveals targeting of myosin XVa-GFP to the dynamic actin region at the tips of filopodia. In a wild-type mouse, during auditory and vestibular hair cell development, myosin XVa appears at the tips of stereocilia at the time when the hair bundle begins to develop its characteristic staircase pattern. We propose that myosin XVa is essential for the graded elongation of stereocilia during their functional maturation.