Chhatre Aditya, Stepanek Ludek, Nievergelt Adrian Pascal, Alvarez Viar Gonzalo, Diez Stefan, Pigino Gaia
Cluster of Excellence Physics of Life, TUD Dresden University of Technology, 01062, Dresden, Germany.
Max Planck Institute of Molecular Cell Biology and Genetics, 01307, Dresden, Germany.
Nat Commun. 2025 Jan 26;16(1):1055. doi: 10.1038/s41467-025-56098-0.
Cilia assembly and function rely on the bidirectional transport of components between the cell body and ciliary tip via Intraflagellar Transport (IFT) trains. Anterograde and retrograde IFT trains travel along the B- and A-tubules of microtubule doublets, respectively, ensuring smooth traffic flow. However, the mechanism underlying this segregation remains unclear. Here, we test whether tubulin detyrosination (enriched on B-tubules) and tyrosination (enriched on A-tubules) have a role in IFT logistics. We report that knockout of tubulin detyrosinase VashL in Chlamydomonas reinhardtii causes frequent IFT train stoppages and impaired ciliary growth. By reconstituting IFT train motility on de-membranated axonemes and synthetic microtubules, we show that anterograde and retrograde trains preferentially associate with detyrosinated and tyrosinated microtubules, respectively. We propose that tubulin tyrosination/detyrosination is crucial for spatial segregation and collision-free IFT train motion, highlighting the significance of the tubulin code in ciliary transport.
纤毛的组装和功能依赖于通过鞭毛内运输（IFT）列车在细胞体和纤毛顶端之间进行的双向成分运输。顺行和逆行的IFT列车分别沿着微管二联体的B微管和A微管移动，以确保顺畅的运输流。然而，这种分离背后的机制仍不清楚。在这里，我们测试了微管蛋白去酪氨酸化（在B微管上富集）和酪氨酸化（在A微管上富集）是否在IFT物流中起作用。我们报告说，莱茵衣藻中微管蛋白去酪氨酸酶VashL的敲除会导致IFT列车频繁停止和纤毛生长受损。通过在去膜轴丝和合成微管上重建IFT列车的运动，我们表明顺行和逆行列车分别优先与去酪氨酸化和酪氨酸化的微管结合。我们提出，微管蛋白酪氨酸化/去酪氨酸化对于空间分离和无碰撞的IFT列车运动至关重要，突出了微管蛋白编码在纤毛运输中的重要性。
