The novel testicular enrichment protein Cfap58 is required for Notch-associated ciliogenesis
The novel testicular enrichment protein Cfap58 is required for Notch-associated ciliogenesis
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Notch 相关纤毛发生需要新型睾丸富集蛋白 Cfap58
DOI：
10.1042/bsr20192666
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发表时间：
2020-01-17
影响因子：
4
通讯作者：
Sun, Fei
中科院分区：
文献类型：
--
作者：
Li, Zheng-Zheng;Zhao, Wen-Long;Sun, Fei
摘要纤毛和鞭毛是重要的细胞器，具有保守的内部结构和不同的发育生理过程。虽然结构的核心成分与数千种参与纤毛或鞭毛形成的相关蛋白质共享，但我们假设一些未知的蛋白质，如外致密纤维2（ODF 2/Cenexin）在这些细胞器中执行不同的功能。在本研究中，我们确定了几个未知的蛋白质，通过质谱相互作用组分析Odf 2/Cenexin蛋白。我们进一步研究了一种名为纤毛和鞭毛相关蛋白58（Cfap 58）的蛋白在培养的星形胶质细胞和精子鞭毛中的表达模式和功能。生物化学分析和药物施用研究的组合的结果揭示，Cfap 58是睾丸富集蛋白，其表现出与Odf 2/Cenexin蛋白相似的定位，并且是通过调节Notch信号传导途径而使初级纤毛和精子中段伸长所需的。然而，在Cfap 58敲低细胞中，细胞周期相关功能和Odf 2/Cenexin在母亲中心粒中的定位没有改变。这些发现表明Cfap 58可能部分被Odf 2/Cenexin蛋白募集，并且对于纤毛和鞭毛组装是不可或缺的。这些数据为我们提供了一个更好的了解纤毛和鞭毛伸长，并可能有助于确定新的目标所造成的疾病Notch介导的纤毛病变和鞭毛异常。
Abstract Cilia and flagella are critical organelles with conserved internal structures and diverse developmental and physiological processes according to cell type. Although the core components of structures are shared with thousands of associated proteins involved in cilia or flagella formation, we hypothesized that some unknown proteins, such as outer dense fiber 2 (Odf2/Cenexin) perform distinct functions in these organelles. In the present study, we identified several uncharacterized proteins through mass spectrometry interactome analysis of Odf2/Cenexin proteins. We further examined the expression patterns and functions of a protein named cilia and flagella associated protein 58 (Cfap58) in cultured astrocytes and sperm flagella. The results of a combination of biochemical analyses and drug administration studies reveal that Cfap58 is a testis-enrichment protein that exhibits similar localization to Odf2/Cenexin proteins and is required for the elongation of the primary cilium and sperm midpiece via modulation of the Notch signaling pathway. However, the cell cycle-related functions and localization of Odf2/Cenexin in the mother centriole were not altered in Cfap58 knockdown cells. These findings indicate that Cfap58 may be partially recruited by Odf2/Cenexin proteins and is indispensable for the cilia and flagellar assembly. These data provide us with a better understanding of ciliogenesis and flagellar elongation and may aid in identifying new targets for diseases caused by Notch-mediated ciliopathies and flagellar abnormalities.