@article{161b5d84500c4b0b871c2926f2d926d5,
title = "Spatiotemporal manipulation of ciliary glutamylation reveals its roles in intraciliary trafficking and Hedgehog signaling",
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.",
author = "Hong, {Shi Rong} and Wang, {Cuei Ling} and Huang, {Yao Shen} and Chang, {Yu Chen} and Chang, {Ya Chu} and Pusapati, {Ganesh V.} and Lin, {Chun Yu} and Ning Hsu and Cheng, {Hsiao Chi} and Chiang, {Yueh Chen} and Huang, {Wei En} and Shaner, {Nathan C.} and Rajat Rohatgi and Takanari Inoue and Lin, {Yu Chun}",
note = "Funding Information: We thank Dr. W. James Nelson (Stanford University) for the MAP4m construct, Dr. Gregory J. Pazour (University of Massachusetts Medical School) for the IFT88 and Kif3B constructs, Dr. Maarten F. Bijlsma and Dr. Helene Damhofer (University of Amsterdam) for the GBS–GFP construct, Dr. Koji Ikegami (Hamamatsu University School of Medicine) for the CCP5 construct, Dr. Carsten Janke (Institut Curie) for the TTLL6 construct, and Dr. Jin-Wu Tsai (National Yang-Ming University) for the Patched1-YFP construct. We also thank Dr. Kristen Verhey (University of Michigan Medical School) for helpful discussions. We are grateful to Dr. Koji Ikegami (Hamamatsu University School of Medicine) for critical reading of the manuscript, as well as Robert DeRose for writing suggestions. We thank Emily Su (Johns Hopkins University) for assistance with experiments and Dr. Tasuku Ueno (University of Tokyo) for the synthesis of GA3-AM. This study was supported in part by the National Institutes of Health (GM105448 and GM118082 to R.R.; GM109984 to N.C.S.; R01DK102910 to T. I.), the Ministry of Science and Technology (MOST), Taiwan (MOST 104-2311-B-007-001, MOST 105-2628-B-007-001-MY3, and Program for Translational Innovation of Biopharma-ceutical Development–Technology Supporting Platform Axis–nMACS imaging No. 107-0210-01-19-04 to Y.C.L.), and start-up funding from National Tsing Hua University to Y. C.L. Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-018-03952-z",
language = "English (US)",
volume = "9",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}