论文
论文标题: Ciliogenesis requires sphingolipid-dependent membrane and axoneme interaction
作者: Wu, Dou; Huang, Jingying; Zhu, Hao; Chen, Zhe; Chai, Yongping; Ke, Jingyi; Lei, Kexin; Peng, Zhao; Zhang, Ranhao; Li, Xueming; Huang, Kaiyao; Li, Wei; Zhao, Chengtian; Ou, Guangshuo
出版刊物: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
出版日期: AUG 2
出版年份: 2022
卷/期:
DOI: 10.1073/pnas.2201096119
论文摘要: Cilium formation and regeneration requires new protein synthesis, but the underlying cytosolic translational reprogramming remains largely unknown. Using ribosome footprinting, we performed global translatome profiling during cilia regeneration in Chlamydomonas and uncovered that flagellar genes undergo an early transcriptional activation but late translational repression. This pattern guided our identification of sphingolipid metabolism enzymes, including serine palmitoyltransferase (SPT), as essential regulators for ciliogenesis. Cryo-electron tomography showed that ceramide loss abnormally increased the membrane-axoneme distance and generated bulged cilia. We found that ceramides interact with intraflagellar transport (IFT) particle proteins that IFT motors transport along axoneme microtubules (MTs), suggesting that ceramide-IFT particle-IFT motor-MT interactions connect the ciliary membrane with the axoneme to form rod-shaped cilia. SPT-deficient vertebrate cells were defective in ciliogenesis, and SPT mutations from patients with hereditary sensory neuropathy disrupted cilia, which could be restored by sphingolipid supplementation. These results reveal a conserved role of sphingolipid in cilium formation and link compromised sphingolipid production with ciliopathies.
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