FCHSD1 and FCHSD2 are expressed in hair cell stereocilia and cuticular plate and regulate actin polymerization in vitro.

FCHSD1 and FCHSD2 are expressed in hair cell stereocilia and cuticular plate and regulate actin polymerization in vitro.
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FCHSD1 和 FCHSD2 在毛细胞立体纤毛和角质板中表达并调节体外肌动蛋白聚合

DOI:
10.1371/journal.pone.0056516
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Xu Z
Xu Z
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cao H;Yin X;Cao Y;Jin Y;Wang S;Kong Y;Chen Y;Gao J;Heller S;Xu Z

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哺乳动物FCHSD1和FCHSD2是同源蛋白,在其羧基末端附近含有一个氨基末端的F-bar结构域和两个SH3结构域。我们在此报道了FCHSD1和FCHSD2在小鼠耳蜗感毛细胞中的表达。FCHSD1主要定位于角质板,而FCHSD2主要沿立体纤毛呈点状分布。NWK是果蝇FCHSD1和FCHSD2的同源同源基因,可以与WSP结合,在F-肌动蛋白组装中发挥重要作用。我们发现,与果蝇的同源物一样,FCHSD2与果蝇WSP的哺乳动物同源基因WASP和N-WASP相互作用,并在体外刺激F-肌动蛋白的组装。相反,FCHSD1不结合WASP或N-WASP,在体外测试时也不能刺激F-肌动蛋白组装。然而,我们发现FCHSD1通过其F-bar结构域与排序连接蛋白9(SNX9)的SH3结构域结合,SNX9是一种特性良好的bar蛋白,已被证明促进WASP-Arp2/3依赖的F-肌动蛋白聚合。FCHSD1显著增强SNX9‘S依赖的F-肌动蛋白聚合活性。在毛细胞中,SNX9与FCHSD1共定位于角质板。我们的结果提示,FCHSD1和FCHSD2可以调节F-肌动蛋白在毛细胞立体纤毛和角质板的组装或维持。
Mammalian FCHSD1 and FCHSD2 are homologous proteins containing an amino-terminal F-BAR domain and two SH3 domains near their carboxyl-termini. We report here that FCHSD1 and FCHSD2 are expressed in mouse cochlear sensory hair cells. FCHSD1 mainly localizes to the cuticular plate, whereas FCHSD2 mainly localizes along the stereocilia in a punctuate pattern. Nervous Wreck (Nwk), the Drosophila ortholog of FCHSD1 and FCHSD2, has been shown to bind Wsp and play an important role in F-actin assembly. We show that, like its Drosophila counterpart, FCHSD2 interacts with WASP and N-WASP, the mammalian orthologs of Drosophila Wsp, and stimulates F-actin assembly in vitro. In contrast, FCHSD1 doesn’t bind WASP or N-WASP, and can’t stimulate F-actin assembly when tested in vitro. We found, however, that FCHSD1 binds via its F-BAR domain to the SH3 domain of Sorting Nexin 9 (SNX9), a well characterized BAR protein that has been shown to promote WASP-Arp2/3-dependent F-actin polymerization. FCHSD1 greatly enhances SNX9’s WASP-Arp2/3-dependent F-actin polymerization activity. In hair cells, SNX9 was detected in the cuticular plate, where it colocalizes with FCHSD1. Our results suggest that FCHSD1 and FCHSD2 could modulate F-actin assembly or maintenance in hair cell stereocilia and cuticular plate.
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发表时间: 1997-01-27
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