Spatiotemporal manipulation of ciliary glutamylation reveals its roles in intraciliary trafficking and Hedgehog signaling
Shi-Rong Hong,
Cuei-Ling Wang,
Yao-Shen Huang,
Yu-Chen Chang,
Ya-Chu Chang,
Ganesh V. Pusapati,
Chun-Yu Lin,
Ning Hsu,
Hsiao-Chi Cheng,
Yueh-Chen Chiang,
Wei-En Huang,
Nathan C. Shaner,
Rajat Rohatgi,
Takanari Inoue () and
Yu-Chun Lin ()
Additional contact information
Shi-Rong Hong: National Tsing Hua University
Cuei-Ling Wang: National Tsing Hua University
Yao-Shen Huang: National Tsing Hua University
Yu-Chen Chang: National Tsing Hua University
Ya-Chu Chang: National Tsing Hua University
Ganesh V. Pusapati: Stanford University School of Medicine
Chun-Yu Lin: National Tsing Hua University
Ning Hsu: National Tsing Hua University
Hsiao-Chi Cheng: National Tsing Hua University
Yueh-Chen Chiang: National Tsing Hua University
Wei-En Huang: National Tsing Hua University
Nathan C. Shaner: The Scintillon Institute
Rajat Rohatgi: Stanford University School of Medicine
Takanari Inoue: Johns Hopkins University
Yu-Chun Lin: National Tsing Hua University
Nature Communications, 2018, vol. 9, issue 1, 1-13
Abstract:
Abstract Tubulin post-translational modifications (PTMs) occur spatiotemporally throughout cells and are suggested to be involved in a wide range of cellular activities. However, the complexity and dynamic distribution of tubulin PTMs within cells have hindered the understanding of their physiological roles in specific subcellular compartments. Here, we develop a method to rapidly deplete tubulin glutamylation inside the primary cilia, a microtubule-based sensory organelle protruding on the cell surface, by targeting an engineered deglutamylase to the cilia in minutes. This rapid deglutamylation quickly leads to altered ciliary functions such as kinesin-2-mediated anterograde intraflagellar transport and Hedgehog signaling, along with no apparent crosstalk to other PTMs such as acetylation and detyrosination. Our study offers a feasible approach to spatiotemporally manipulate tubulin PTMs in living cells. Future expansion of the repertoire of actuators that regulate PTMs may facilitate a comprehensive understanding of how diverse tubulin PTMs encode ciliary as well as cellular functions.
Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03952-z
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DOI: 10.1038/s41467-018-03952-z
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