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Current topics of functional links between primary cilia and cell cycle

机译：原发性纤毛和细胞周期之间功能性联系的最新主题

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Primary cilia, microtubule-based sensory structures, orchestrate various critical signals during development and tissue homeostasis. In view of the rising interest into the reciprocal link between ciliogenesis and cell cycle, we discuss here several recent advances to understand the molecular link between the individual step of ciliogenesis and cell cycle control. At the onset of ciliogenesis (the transition from centrosome to basal body), distal appendage proteins have been established as components indispensable for the docking of vesicles at the mother centriole. In the initial step of axonemal extension, CP110, Ofd1, and trichoplein, key negative regulators of ciliogenesis, are found to be removed by a kinase-dependent mechanism, autophagy, and ubiquitin–proteasome system, respectively. Of note, their disposal functions as a restriction point to decide that the axonemal nucleation and extension begin. In the elongation step, Nde1, a negative regulator of ciliary length, is revealed to be ubiquitylated and degraded by CDK5-SCFFbw7 in a cell cycle-dependent manner. With regard to ciliary length control, it has been uncovered in flagellar shortening of Chlamydomonas that cilia itself transmit a ciliary length signal to cytoplasm. At the ciliary resorption step upon cell cycle re-entry, cilia are found to be disassembled not only by Aurora A-HDAC6 pathway but also by Nek2-Kif24 and Plk1-Kif2A pathways through their microtubule-depolymerizing activity. On the other hand, it is becoming evident that the presence of primary cilia itself functions as a structural checkpoint for cell cycle re-entry. These data suggest that ciliogenesis and cell cycle intimately link each other, and further elucidation of these mechanisms will contribute to understanding the pathology of cilia-related disease including cancer and discovering targets of therapeutic interventions.
机译：主要的纤毛，基于微管的感觉结构，在发育和组织稳态过程中协调各种关键信号。鉴于人们对纤毛生成和细胞周期之间的相互联系的兴趣日益浓厚，我们在这里讨论了一些最新进展，以了解纤毛生成和细胞周期控制的各个步骤之间的分子联系。在纤毛发生（从中心体到基体的转变）开始时，远端的附件蛋白已被确定为囊泡在母体中心对接所必需的成分。在轴突扩展的初始步骤中，发现纤毛生成的关键负调节剂CP110，Ofd1和木瓜蛋白分别被激酶依赖性机制，自噬和泛素-蛋白酶体系统清除。值得注意的是，它们的处置是决定轴突成核和延伸开始的限制点。在延伸步骤中，显示出Nde1（纤毛长度的负调节剂）被CDK5-SCFFbw7以细胞周期依赖性的方式泛素化并降解。关于纤毛长度控制，在衣藻鞭毛缩短中已经发现纤毛本身将纤毛长度信号传递至细胞质。在细胞周期重新进入的纤毛吸收步骤中，发现纤毛不仅通过Aurora A-HDAC6途径被分解，而且通过其微管解聚活性被Nek2-Kif24和Plk1-Kif2A途径分解。另一方面，越来越明显的是，初级纤毛本身的存在是细胞周期再进入的结构检查点。这些数据表明，纤毛形成和细胞周期彼此紧密联系，进一步阐明这些机制将有助于理解纤毛相关疾病（包括癌症）的病理学，并发现治疗干预的靶标。

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