Vlgr1 is required for proper stereocilia maturation of cochlear hair cells
Vlgr1 is required for proper stereocilia maturation of cochlear hair cells
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DOI：
10.1111/j.1365-2443.2007.01046.x
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发表时间：
2007-02-01
期刊：
影响因子：
2.1
通讯作者：
Sato, Makoto
中科院分区：
文献类型：
--
作者：
Yagi, Hideshi;Tokano, Hisashi;Sato, Makoto
超大型G蛋白偶联受体（Vlgr 1b）是已知最大的G蛋白偶联受体。其功能尚不清楚，尽管已知缺失Vlgr 1（Vlgr 1b与其他剪接变体Vlgr 1c、Vlgr 1d和Vlgr 1 e）的小鼠表现出听源性癫痫易感性，并且据报道VLGR 1是导致Usher 2C型综合征的基因。我们在这里证明，Vlgr 1突变的小鼠患有听力缺陷，因为内耳功能障碍，如听觉脑干反应（ABR）和畸变产物耳声发射（DPOAE）所示。Vlgr 1在围生期发育的毛细胞中表达，共聚焦显微镜观察到翻译产物定位于毛细胞静纤毛基部。免疫电镜显示，Vlgr 1定位仅限于静纤毛基部，距离毛细胞顶面约200-400 nm。Vlgr 1突变的小鼠表现出静纤毛畸形;耳蜗毛束在出生时明显正常，但在出生后第8天变得紊乱。此外，突变小鼠的静纤毛变得倾斜和混乱。这些结果表明Vlgr 1的缺失导致静纤毛形成的异常发育。
Very large G-protein coupled receptor (Vlgr1b) is the largest known G-protein coupled receptor. Its function is unknown, although mice with deletion of Vlgr1 (Vlgr1b together with other splicing variants, Vlgr1c, Vlgr1d and Vlgr1e) are known to exhibit audiogenic seizure susceptibility and VLGR1 is reported to be the gene responsible for Usher type 2C syndrome. We demonstrated here that Vlgr1-mutated mice suffered from a hearing defect because of inner ear dysfunction, as indicated by auditory brainstem response (ABR) and distortion product oto-acoustic emissions (DPOAE). The expression of Vlgr1 was identified in the developing hair cells perinatally, and the translated products were seen to be localized in the base of stereocilia on hair cells using confocal microscopy. This Vlgr1 localization was limited to the base of stereocilia within approximately 200-400 nm from the apical surface of hair cells, as shown by immunoelectron microscopy. The Vlgr1-mutated mice exhibited malformation of the stereocilia; the cochlear hair bundles were apparently normal at birth but then became disarranged at postnatal day 8. Furthermore, the stereocilia in the mutant mice became slanted and disarranged thereafter. These results indicate that loss of Vlgr1 resulted in abnormal development of stereocilia formation.