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ERK7 通过与 Dishevelled 合作磷酸化肌动蛋白调节因子 CapZIP 来调节纤毛生成。

ERK7 regulates ciliogenesis by phosphorylating the actin regulator CapZIP in cooperation with Dishevelled.

机构信息

Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.

出版信息

Nat Commun. 2015 Mar 31;6:6666. doi: 10.1038/ncomms7666.

Abstract

Cilia are essential for embryogenesis and maintenance of homeostasis, but little is known about the signalling pathways that regulate ciliogenesis. Here, we identify ERK7, an atypical mitogen-activated protein kinase, as a key regulator of ciliogenesis. ERK7 is strongly expressed in ciliated tissues of Xenopus embryos. ERK7 knockdown markedly diminishes both the number and the length of cilia in multiciliated cells, and it inhibits the apical migration of basal bodies. Moreover, ERK7 knockdown results in a loss of the apical actin meshwork, which is required for the proper migration of basal bodies. We find that the actin regulator CapZIP, which has been shown to regulate ciliogenesis in a phosphorylation-dependent manner, is an ERK7 substrate, and that Dishevelled, which has also been shown to regulate ciliogenesis, facilitates ERK7 phosphorylation of CapZIP through binding to both ERK7 and CapZIP. Collectively, these results identify an ERK7/Dishevelled/CapZIP axis that regulates ciliogenesis.

摘要

纤毛对于胚胎发生和体内平衡的维持至关重要,但调控纤毛发生的信号通路知之甚少。在这里,我们鉴定出 ERK7,一种非典型的丝裂原活化蛋白激酶,是纤毛发生的关键调节因子。ERK7 在非洲爪蟾胚胎的纤毛组织中强烈表达。ERK7 敲低显著减少了多纤毛细胞中纤毛的数量和长度,并抑制了基体的顶端迁移。此外,ERK7 敲低导致顶端肌动蛋白网格的丢失,这对于基体的正确迁移是必需的。我们发现,肌动蛋白调节因子 CapZIP 已被证明以磷酸化依赖的方式调控纤毛发生,是 ERK7 的底物,而 Dishevelled 也被证明调控纤毛发生,通过与 ERK7 和 CapZIP 结合促进 ERK7 对 CapZIP 的磷酸化。总的来说,这些结果确定了一个 ERK7/Dishevelled/CapZIP 轴,它调节纤毛发生。

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