Chen Qingxia, Zhao Huijie, Pan Xinwen, Fang Chuyu, Qiu Benhua, Guo Jingting, Yan Xiumin, Zhu Xueliang
Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Institute of Early Life Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China.
J Mol Cell Biol. 2025 Jan 30;16(8). doi: 10.1093/jmcb/mjae031.
Cilia's back-and-forth beat pattern requires a central pair (CP) of microtubules. However, the mechanism by which the CP is upheld above the transition zone (TZ) remains unclear. Here, we showed that a rod-like substructure marked by Cep131 and ciliary Centrin serves as a polarized CP-supporting foundation. This CP-foundation (CPF) was assembled independently of the CP during ciliogenesis in mouse ependymal cells. It protruded from the distal end of the basal body out of the TZ to enwrap the proximal end of the CP. Through proximity labeling, we identified 26 potential CPF components, among which Ccdc148 specifically localized at the proximal region of Centrin-decorated CPF and was complementary to the Cep131-enriched distal region. Cep131 deficiency abolished the CPF, resulting in CP penetration into the TZ. Consequently, cilia became prone to ultrastructural abnormality and paralysis, and Cep131-deficient mice were susceptible to late-onset hydrocephalus. In addition to Centrin, phylogenetic analysis also indicated conservations of Ccdc131 and Ccdc148 from protists to mammals, suggesting that the CPF is an evolutionarily conserved multicomponent CP-supporting platform in cilia.
纤毛的来回摆动模式需要一对中央微管（CP）。然而，CP在过渡区（TZ）上方得以维持的机制仍不清楚。在此，我们表明，由Cep131和纤毛中心蛋白标记的棒状亚结构作为一个极化的CP支撑基础。在小鼠室管膜细胞纤毛发生过程中，这个CP基础（CPF）独立于CP组装而成。它从基体远端伸出TZ，包裹CP的近端。通过邻近标记，我们鉴定出26种潜在的CPF成分，其中Ccdc148特异性定位于中心蛋白标记的CPF近端区域，与富含Cep131的远端区域互补。Cep131缺陷消除了CPF，导致CP穿透进入TZ。因此，纤毛易于出现超微结构异常和麻痹，且Cep131缺陷小鼠易患迟发性脑积水。除了中心蛋白，系统发育分析还表明从原生生物到哺乳动物Ccdc131和Ccdc148具有保守性，这表明CPF是纤毛中一个进化上保守的多成分CP支撑平台。
