ACF7 Is a Hair-Bundle Antecedent, Positioned to Integrate Cuticular Plate Actin and Somatic Tubulin

ACF7 Is a Hair-Bundle Antecedent, Positioned to Integrate Cuticular Plate Actin and Somatic Tubulin
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DOI:
10.1523/jneurosci.1880-13.2014
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发表时间:
2014-01-01
影响因子:
5.3
通讯作者:
McDermott, Brian M., Jr.
McDermott, Brian M., Jr.
中科院分区:
医学1区
文献类型:
--
作者:
Antonellis, Patrick J.;Pollock, Lana M.;McDermott, Brian M., Jr.

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机械敏感毛束的精确形态需要肌动蛋白和微管网络的无缝整合。在这里,我们确定Acf7a(肌动蛋白交联家族蛋白7a)是一种定位为连接毛细胞中这些不同的细胞骨架网络的蛋白质。通过对斑马鱼Acf7a-Citine融合蛋白的成像和对前庭和耳蜗鼠毛细胞的免疫标记,我们发现Acf7a和ACF7被包围、位于角质板(CP)下并交织在角质板(CP)中,它们还包围着动纤毛的基底层。在耳蜗毛细胞中,ACF7的定位是分级的,在每个穹隆附近浓度最高-在包含基底体的CP区域中没有F-肌动蛋白的区域。在毛细胞发育和再生过程中,Acf7a先于毛束和CP的形成。最后,电子断层扫描显示,微管的末端插入到CP中,并装饰有连接微管和CP的丝状连接物。这些观察结果与ACF7是一种连接蛋白是一致的,ACF7可能在毛束形成的早期塑造毛细胞的细胞骨架。
The precise morphology of the mechanosensitive hair bundle requires seamless integration of actin and microtubule networks. Here, we identify Acf7a (actin crosslinking family protein 7a) as a protein positioned to bridge these distinct cytoskeletal networks in hair cells. By imaging Acf7a-Citrine fusion protein in zebrafish and immunolabeling of vestibular and cochlear mouse hair cells, we show that Acf7a and ACF7 circumscribe, underlie, and are interwoven into the cuticular plate (CP), and they also encircle the basal body of the kinocilium. In cochlear hair cells, ACF7 localization is graded, with the highest concentration near each fonticulus-an area free of F-actin in the region of the CP that contains the basal body. During hair-cell development and regeneration, Acf7a precedes formation of the hair bundle and CP. Finally, electron tomography demonstrates that the ends of microtubules insert into the CP and are decorated with filamentous linkers connecting microtubules to the CP. These observations are consistent with ACF7 being a linker protein, which may shape the cytoskeleton of the hair cell early during hair-bundle genesis.