Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-03952-z
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Funding
- National Institutes of Health [GM105448, GM118082, GM109984, R01DK102910]
- Ministry of Science and Technology (MOST), Taiwan [MOST 104-2311-B-007-001, MOST 105-2628-B-007-001-MY3]
- Ministry of Science and Technology (MOST), Taiwan (Program for Translational Innovation of Biopharmaceutical Development-Technology Supporting Platform Axis-nMACS imaging) [107-0210-01-19-04]
- National Tsing Hua University
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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.
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