Stereocilia defects in the sensory hair cells of the inner ear in mice deficient in integrin α8β1
Stereocilia defects in the sensory hair cells of the inner ear in mice deficient in integrin α8β1
复制标题
DOI：
10.1038/74286
复制
发表时间：
2000-04-01
期刊：
影响因子：
30.8
通讯作者：
Müller, U
中科院分区：
文献类型：
--
作者：
Evans, AL;Müller, U
哺乳动物的内耳包含用于检测声音和加速度的器官，分别是耳蜗和前庭。这些器官的神经上皮内的机械感觉毛细胞将声波或头部运动产生的机械力转换为神经信号。毛细胞缺陷导致耳聋和平衡缺陷（1-3）。毛细胞具有静纤毛，其对于机械感觉是不可或缺的，但是调节静纤毛形成的分子机制知之甚少（4-6）。我们在这里显示，整合素α 8 β 1，其配体纤连蛋白和整合素调节的粘着斑激酶（FAK）共定位于顶端毛细胞表面，静纤毛正在形成。在Itga 8（编码α 8亚基;参考文献7）靶向突变的纯合子小鼠中，这种共定位受到干扰，椭圆囊（前庭亚室）中的毛细胞缺乏静纤毛或含有畸形的静纤毛。大多数整合素α 8 β 1缺陷小鼠出生后不久就死于肾缺陷。许多幸存者都有平衡困难，这与内耳的结构缺陷相一致。我们的数据表明，整合素α 8 β 1，和潜在的其他整合素，调节毛细胞分化和静纤毛成熟。影响基质分子的突变导致遗传形式的内耳疾病（1- 3，8），整合素可能介导基质分子在耳中的某些作用：因此，整合素基因的突变也可能导致内耳疾病。
The mammalian inner ear contains organs for the detection of sound and acceleration, the cochlea and the vestibule, respectively. Mechanosensory hair cells within the neuroepithelia of these organs transduce mechanical force generated by sound waves or head movements into neuronal signals. Defects in hair cells lead to deafness and balance defects(1-3). Hair cells have stereocilia that are indispensable for mechanosensation, but the molecular mechanisms regulating stereocilia formation are poorly understood(4-6). We show here that integrin alpha 8 beta 1, its ligand fibronectin and the integrin-regulated focal adhesion kinase (FAK) co-localize to the apical hair-cell surface where stereocilia are forming. In mice homozygous for a targeted mutation of Itga8 (encoding the alpha 8 subunit; ref. 7), this co-localization is perturbed and hair cells in the utricle, a vestibular subcompartment, lack stereocilia or contain malformed stereocilia. Most integrin-alpha 8 beta 1-deficient mice die soon after birth due to kidney defects. Many of the survivors have difficulty balancing, consistent with the structural defects of the inner ear. Our data suggest that integrin alpha 8 beta 1, and potentially other integrins, regulates hair-cell differentiation and stereocilia maturation. Mutations affecting matrix molecules cause inherited forms of inner ear disease(1-3,8) and integrins may mediate some effects of matrix molecules in the ear: thus, mutations in integrin genes may lead to inner-ear diseases as well.