Shankar Sahana, Hsu Zi-Ting, Ezquerra Artur, Li Chien-Chien, Huang Tzu-Lun, Coyaud Etienne, Viais Ricardo, Grauffel Cédric, Raught Brian, Lim Carmay, Lüders Jens, Tsai Su-Yi, Hsia Kuo-Chiang
Molecular and Cell Biology, Taiwan International Graduate Program, Academia Sinica and National Defense Medical Center, Taipei 11490, Taiwan; Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
Department of Life Science, National Taiwan University, Taipei 10617, Taiwan.
Cell Rep. 2022 Nov 15;41(7):111642. doi: 10.1016/j.celrep.2022.111642.
The primary cilium, a microtubule-based sensory organelle, undergoes cycles of assembly and disassembly that govern the cell cycle progression critical to cell proliferation and differentiation. Although cilia assembly has been studied extensively, the molecular mechanisms underlying cilia disassembly are less well understood. Here, we uncover a γ-tubulin ring complex (γ-TuRC)-dependent pathway that promotes cilia disassembly and thereby prevents cilia formation. We further demonstrate that Kif2A, a kinesin motor that bears microtubule-depolymerizing activity, is recruited to the cilium basal body in a γ-TuRC-dependent manner. Our mechanistic analyses show that γ-TuRC specifically recruits Kif2A via the GCP2 subunit and its binding partner Mzt2. Hence, despite the long-standing view that γ-TuRC acts mainly as a microtubule template, we illustrate that its functional heterogeneity at the basal body facilitates both microtubule nucleation and Kif2A recruitment-mediated regulation of ciliogenesis, ensuring cell cycle progression.
初级纤毛是一种基于微管的感觉细胞器，经历组装和解聚循环，这些循环控制着对细胞增殖和分化至关重要的细胞周期进程。尽管纤毛组装已被广泛研究，但纤毛解聚的分子机制仍不太清楚。在这里，我们发现了一种依赖γ-微管蛋白环复合物（γ-TuRC）的途径，该途径促进纤毛解聚，从而防止纤毛形成。我们进一步证明，具有微管解聚活性的驱动蛋白Kif2A以γ-TuRC依赖的方式被招募到纤毛基体。我们的机制分析表明，γ-TuRC通过GCP2亚基及其结合伙伴Mzt2特异性招募Kif2A。因此，尽管长期以来认为γ-TuRC主要作为微管模板发挥作用，但我们表明其在基体的功能异质性促进了微管成核以及Kif2A招募介导的纤毛发生调控，确保细胞周期进程。
