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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Whirlin complexes with p55 at the stereocilia tip during hair cell development
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Whirlin complexes with p55 at the stereocilia tip during hair cell development

机译：毛细胞发育过程中，Whirlin与p55在立体纤毛末端复合

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摘要

Hearing in mammals depends upon the proper development of actin-filled stereocilia at the hair cell surface in the inner ear. Whirlin, a PDZ domain-containing protein, is expressed at stereocilia tips and, by virtue of mutations in the whirlin gene, is known to play a key role in stereocilia development. We show that whirlin interacts with the membrane-associated guanylate kinase (MAGUK) protein, erythrocyte protein p55 (p55). p55 is expressed in outer hair cells in long stereocilia that make up the stereocilia bundle as well as surrounding shorter stereocilia structures. p55 interacts with protein 4.1 R in erythrocytes, and we find that 4.1 R is also expressed in stereocilia structures with an identical pattern to p55. Mutations in the whirlin gene (whirler) and in the myosin XVa gene (shaker2) affect stereocilia development and lead to early ablation of p55 and 4.1R labeling of stereocilia. The related MAGUK protein Ca2+-calmodulin serine kinase (CASK) is also expressed in stereocilia in both outer and inner hair cells, where it is confined to the stereocilia bundle. CASK interacts with protein 4.1N in neuronal tissue, and we find that 4.1N is expressed in stereocilia with an identical pattern to CASK. Unlike p55, CASK labeling shows little diminution of labeling in the whirler mutant and is unaffected in the shaker2 mutant. Similarly, expression of 4.1N in stereocilia is unaltered in whirler and shaker2 mutants. p55 and protein 4.1R form complexes critical for actin cytoskeletal assembly in erythrocytes, and the interaction of whirlin with p55 indicates it plays a similar role in hair cell stereocilia.
机译：哺乳动物的听力取决于内耳毛细胞表面充满肌动蛋白的立体纤毛的适当发育。旋转蛋白是一种包含PDZ结构域的蛋白，在纤毛尖端表达，并且由于whirlin基因的突变，已知在纤毛发育中起关键作用。我们显示whirlin与膜相关的鸟苷酸激酶（MAGUK）蛋白，红细胞蛋白p55（p55）相互作用。 p55在构成纤毛束的长形纤毛的外毛细胞中以及周围较短的纤毛结构中表达。 p55与红细胞中的蛋白4.1 R相互作用，并且我们发现4.1 R也以与p55相同的模式在立体纤毛结构中表达。旋转蛋白基因（whirler）和肌球蛋白XVa基因（shaker2）中的突变影响了纤毛虫的发育，并导致早期消融了纤毛虫的p55和4.1R标记。相关的MAGUK蛋白Ca2 +-钙调蛋白丝氨酸激酶（CASK）也表达在外毛细胞和内毛细胞的立体纤毛中，并局限于纤毛束中。 CASK与神经元组织中的蛋白质4.1N相互作用，我们发现4.1N在立体纤毛中表达的方式与CASK相同。与p55不同，CASK标记在whirler突变体中显示的标记几乎没有减少，并且在shaker2突变体中不受影响。同样，在旋转和突变体2突变体中，纤毛虫中4.1N的表达没有改变。 p55和蛋白4.1R形成了对红细胞中肌动蛋白细胞骨架组装至关重要的复合物，并且whirlin与p55的相互作用表明它在毛细胞立体纤毛中起着相似的作用。

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