A new compartment at stereocilia tips defined by spatial and temporal patterns of myosin IIIa expression
A new compartment at stereocilia tips defined by spatial and temporal patterns of myosin IIIa expression
复制标题
DOI：
10.1523/jneurosci.2812-06.2006
复制
发表时间：
2006-10-04
影响因子：
5.3
通讯作者：
Kachar, Bechara
中科院分区：
文献类型：
--
作者：
Schneider, Mark E.;Dose, Andrea C.;Kachar, Bechara
III类肌球蛋白是含有n端激酶结构域和c端肌动蛋白结合结构域的运动蛋白。我们发现肌球蛋白IIIa与非综合征性进行性听力损失有关，它位于立体纤毛尖端。在立体纤毛成熟过程中，Myosin IIIa在立体纤毛尖端周围以针状模式逐渐积累，这与Myosin XVa的帽状定位和Myosin Ic的轴状定位不同。绿色荧光蛋白(GFP)-myosin IIIa功能域的缺失突变体的过表达表明，立体纤毛尖端定位需要运动结构域，而不是肌动蛋白结合的尾部结构域。激酶结构域的缺失导致立纤毛伸长和立纤毛尖端膨出。针状定位和肌球蛋白IIIa对纤毛形状的影响揭示了纤毛远端以前未被识别的分子室，这是肌动蛋白聚合的位置以及机电转导装置的操作。
Class III myosins are motor proteins that contain an N-terminal kinase domain and a C-terminal actin-binding domain. We show that myosin IIIa, which has been implicated in nonsyndromic progressive hearing loss, is localized at stereocilia tips. Myosin IIIa progressively accumulates during stereocilia maturation in a thimble-like pattern around the stereocilia tip, distinct from the cap-like localization of myosin XVa and the shaft localization of myosin Ic. Overexpression of deletion mutants for functional domains of green fluorescent protein (GFP)-myosin IIIa shows that the motor domain, but not the actin-binding tail domain, is required for stereocilia tip localization. Deletion of the kinase domain produces stereocilia elongation and bulging of the stereocilia tips. The thimble-like localization and the influence myosin IIIa has on stereocilia shape reveal a previously unrecognized molecular compartment at the distal end of stereocilia, the site of actin polymerization as well as operation of the mechanoelectrical transduction apparatus.