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Abstract：
Cilia are thin cell projections with essential roles in cell motility, fluid movement, sensing, and signaling. They are templated from centrioles that dock against the plasma membrane and subsequently extend their peripheral microtubule array. The molecular mechanisms underpinning cilia assembly are incompletely understood. Cep104 is a key factor involved in cilia formation and length regulation that rides on the ends of elongating and shrinking cilia. It is mutated in Joubert syndrome, a genetically heterogeneous ciliopathy. Here we provide structural and biochemical data that Cep104 contains a tubulin-binding TOG (tumor overexpressed gene) domain and a novel C2HC zinc finger array. Furthermore, we identify the kinase Nek1, another ciliopathy-associated protein, as a potential binding partner of this array. Finally, we show that Nek1 competes for binding to Cep104 with the distal centriole-capping protein CP110. Our data suggest a model for Cep104 activity during ciliogenesis and provide a novel link between Cep104 and Nek1.
摘要：
纤毛是细的细胞突起，在细胞运动中起着重要作用，流体运动,传感,和信号。它们由中心粒模板化，这些中心粒与质膜对接，随后延伸其外围微管阵列。支持纤毛组装的分子机制尚未完全了解。Cep104是纤毛形成和长度调节中涉及的关键因素，它骑在伸长和收缩纤毛的末端。它在Joubert综合征中变异,遗传异质性纤毛病。在这里，我们提供了Cep104包含微管蛋白结合TOG（肿瘤过表达基因）结构域和新型C2HC锌指阵列的结构和生化数据。此外，我们确定了激酶Nek1，另一种纤毛相关蛋白，作为该阵列的潜在结合伙伴。最后,我们显示Nek1与远端中心粒加帽蛋白CP110竞争结合Cep104。我们的数据表明了纤毛发生过程中Cep104活性的模型，并在Cep104和Nek1之间提供了新的联系。
