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, Yu Chun Lin

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number1732
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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