Saito Masaki, Otsu Wataru
Department of Molecular Pharmacology, Tohoku University School of Medicine.
Department of Ophthalmology, Margaret M. Dyson Vision Research Institute, Weill Medical College of Cornell University.
Nihon Yakurigaku Zasshi. 2019;154(4):197-202. doi: 10.1254/fpj.154.197.
Primary cilium is a membrane-protruding sensory organelle, which is organized from a basal body in G/G phase cells. The resorption of primary cilia under specific growth factor stimuli is coupled to cell cycle re-entry and cell proliferation, and the proliferative function is vital for the organization of organs at an embryonic stage. In fact, abnormalities in ciliogenesis and/or cilium-derived signaling lead to malformation of various organs, such as the brain, eyes, nose, ear, heart, lung, liver, kidney, and bones. The inborn genetic disorders are collectively called 〝ciliopathy〟. However, the pathogenesis of the ciliopathies has largely remained unexplained, especially little is known about the cellular machinery that controls the ciliary resorption. Tctex-1 (t-complex testis expressed-1), one of the light chains of cytoplasmic dynein complex, regulates intracellular trafficking along microtubule. Tctex-1 phosphorylated at Thr94 is, in turn, free from the dynein complex to execute dynein-free functions. This review summarizes the current situation of the mechanisms of ciliary resorption with a central focus on the role of phosphorylated Tctex-1.
初级纤毛是一种突出于细胞膜的感觉细胞器,由处于G/G期细胞中的基体组装而成。在特定生长因子刺激下,初级纤毛的解聚与细胞周期重新进入和细胞增殖相关联,并且这种增殖功能对于胚胎期器官的形成至关重要。事实上,纤毛发生和/或纤毛衍生信号传导的异常会导致各种器官畸形,如脑、眼、鼻、耳、心脏、肺、肝脏、肾脏和骨骼。这些先天性遗传疾病统称为“纤毛病”。然而,纤毛病的发病机制在很大程度上仍未得到解释,尤其是对于控制纤毛解聚的细胞机制知之甚少。Tctex-1(t-复合体睾丸表达-1)是胞质动力蛋白复合体的轻链之一,可调节沿微管的细胞内运输。在苏氨酸94处磷酸化的Tctex-1反过来会脱离动力蛋白复合体以执行无动力蛋白功能。本综述总结了纤毛解聚机制的现状,重点关注磷酸化Tctex-1的作用。