EXPRESSION IN COCHLEA AND RETINA OF MYOSIN VIIA, THE GENE-PRODUCT DEFECTIVE IN USHER SYNDROME TYPE 1B
EXPRESSION IN COCHLEA AND RETINA OF MYOSIN VIIA, THE GENE-PRODUCT DEFECTIVE IN USHER SYNDROME TYPE 1B
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DOI：
10.1073/pnas.92.21.9815
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发表时间：
1995-10-10
影响因子：
11.1
通讯作者：
MOOSEKER, MS
中科院分区：
文献类型：
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作者：
HASSON, T;HEINTZELMAN, MB;MOOSEKER, MS
肌球蛋白VIIa是一个新发现的肌动蛋白为基础的马达肌球蛋白超家族成员。最近，肌球蛋白VIIa基因被鉴定为shaker-1（小鼠的隐性耳聋）中的缺陷基因[吉布森，F.，沃尔什，J.，Mburu，P.，Varela，A.，布朗，K。一、Antonio，M.，Beisel，K. W.，钢，K。P. & Brown，S. D. M.（1995）Nature（伦敦）374，62-64]，以及在人类Usher综合征1B型中，一种以先天性耳聋、前庭功能障碍和色素性视网膜炎为特征的遗传性疾病[Well，D.，Blanchard，S.，卡普兰，J.，Guilford，P.，吉布森，F.，沃尔什，J.，Mburu，P.，Varela，A.，Levilliers，J.，韦斯顿，M. D、凯利，P. M.，金伯利，W. J.，Wagenaar，M.，Levi-Acobas，F.，Larget-Piet，D.，Munnich，A.，钢，K。P.，布朗，S。D. M. & Petit，C.（1995）Nature（伦敦）374，60-61]。为了了解肌球蛋白VIIa的正常功能，以及它在缺陷时如何导致这些疾病表型，我们产生了针对这种非常规肌球蛋白尾部的特异性抗体。我们发现肌球蛋白VIIa在耳蜗、视网膜、睾丸、肺和肾中表达。在耳蜗中，肌球蛋白VIIa表达仅限于内毛细胞和外毛细胞，在那里它被发现在顶端静纤毛以及细胞质。在眼睛中，肌球蛋白VIIa由视网膜色素上皮细胞表达，在该细胞类型的顶端肌动蛋白丰富的结构域内富集。肌球蛋白VIIa的细胞特异性定位表明，与Usher综合征相关的失明和耳聋是由于耳蜗毛细胞和视网膜色素上皮细胞内缺乏适当的肌球蛋白VIIa功能。
Myosin VIIa is a newly identified member of the myosin superfamily of actin-based motors. Recently, the myosin VIIa gene was identified as the gene defective in shaker-1, a recessive deafness in mice [Gibson, F., Walsh, J., Mburu, P., Varela, A., Brown, K. A., Antonio, M., Beisel, K. W., Steel, K. P. & Brown, S. D. M. (1995) Nature (London) 374, 62-64], and in human Usher syndrome type 1B, an inherited disease characterized by congenital deafness, vestibular dysfunction, and retinitis pigmentosa [Well, D., Blanchard, S., Kaplan, J., Guilford, P., Gibson, F., Walsh, J., Mburu, P., Varela, A., Levilliers, J., Weston, M. D., Kelley, P. M., Kimberling, W. J., Wagenaar, M., Levi-Acobas, F., Larget-Piet, D., Munnich, A., Steel, K. P., Brown, S. D. M. & Petit, C. (1995) Nature (London) 374, 60-61]. To understand the normal function of myosin VIIa and how it could cause these disease phenotypes when defective, we generated antibodies specific to the tail portion of this unconventional myosin. We found that myosin VIIa was expressed in cochlea, retina, testis, lung, and kidney. In cochlea, myosin VIIa expression was restricted to the inner and outer hair cells, where it was found in the apical stereocilia as well as the cytoplasm. In the eye, myosin VIIa was expressed by the retinal pigmented epithelial cells, where it was enriched within the apical actin-rich domain of this cell type. The cell-specific localization of myosin VIIa suggests that the blindness and deafness associated with Usher syndrome is due to lack of proper myosin VIIa function within the cochlear hair cells and the retinal pigmented epithelial cells.