Twinfilin 2 regulates actin filament lengths in cochlear stereocilia.
Twinfilin 2 regulates actin filament lengths in cochlear stereocilia.
复制标题
DOI：
10.1523/jneurosci.2782-09.2009
复制
发表时间：
2009-12-02
期刊：
影响因子：
--
通讯作者：
Heller S
中科院分区：
文献类型：
--
作者：
Peng AW;Belyantseva IA;Hsu PD;Friedman TB;Heller S
内耳感觉毛细胞将机械刺激转化为电信号。这种转换发生在从细胞顶端表面伸出的对机械敏感的精致发束中。在哺乳动物中，耳蜗毛束由50-100根充满肌动蛋白的立体纤毛组成，它们以楼梯的方式排列成三排。立体纤毛肌动蛋白细丝均匀定向，其带刺的末端朝向立体纤毛尖端。在发育过程中，由于肌动蛋白单体添加到细丝的带刺末端，每个立体纤毛的肌动蛋白核心都经历了延长。在这里，我们表明，在小鼠耳蜗中，倒钩末端封顶蛋白孪infilin 2存在于中、短行立体纤毛的顶端，从出生后第5天开始，这与这些行停止生长的时间段有关。高大的立体纤毛在顶端不显示孪生纤毛蛋白2，在P5和P15之间继续伸长。当我们在LLC/PK1-CL4(CL4)细胞中表达双丝蛋白2时，我们观察到Espin诱导的微绒毛长度缩短，这表明双丝蛋白2在抑制肌动蛋白细丝的伸长方面具有强大的功能。双丝蛋白2在耳蜗内毛细胞中的过表达导致耳蜗体纤毛长度显著缩短。我们的结果提示，双丝蛋白2可能通过限制短排体纤毛的过度伸长，从而维持耳蜗束的成熟阶梯结构，从而调节体毛纤毛的伸长。
Inner ear sensory hair cells convert mechanical stimuli into electrical signals. This conversion happens in the exquisitely mechanosensitive hair bundle that protrudes from the cell's apical surface. In mammals, cochlear hair bundles are composed of 50-100 actin-filled stereocilia, which are organized in three rows in a staircase fashion. Stereocilia actin filaments are uniformly oriented with their barbed ends toward stereocilia tips. During development, the actin core of each stereocilium undergoes elongation due to addition of actin monomers to the barbed ends of the filaments. Here we show that in the mouse cochlea the barbed end capping protein twinfilin 2 is present at the tips of middle and short rows of stereocilia from postnatal day (P) 5 onward, which correlates with a time period when these rows stop growing. The tall stereocilia rows, which do not display twinfilin 2 at their tips, continue to elongate between P5 and P15. When we expressed twinfilin 2 in LLC/PK1-CL4 (CL4) cells, we observed a reduction of espin-induced microvilli length, pointing to a potent function of twinfilin 2 in suppressing the elongation of actin filaments. Overexpression of twinfilin 2 in cochlear inner hair cells resulted in a significant reduction of stereocilia length. Our results suggest that twinfilin 2 plays a role in the regulation of stereocilia elongation by restricting excessive elongation of the shorter row stereocilia thereby maintaining the mature staircase architecture of cochlear hair bundles.