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Editing of endogenous tubulins reveals varying effects of tubulin posttranslational modifications on axonal growth and regeneration.

Yu-Ming Lu | Shan Yan | Shih-Chieh Ti | Chaogu Zheng
eLife | 2024

Tubulin posttranslational modifications (PTMs) modulate the dynamic properties of microtubules and their interactions with other proteins. However, the effects of tubulin PTMs were often revealed indirectly through the deletion of modifying enzymes or the overexpression of tubulin mutants. In this study, we directly edited the endogenous tubulin loci to install PTM-mimicking or -disabling mutations and studied their effects on microtubule stability, neurite outgrowth, axonal regeneration, cargo transport, and sensory functions in the touch receptor neurons of Caenorhabditis elegans. We found that the status of β-tubulin S172 phosphorylation and K252 acetylation strongly affected microtubule dynamics, neurite growth, and regeneration, whereas α-tubulin K40 acetylation had little influence. Polyglutamylation and detyrosination in the tubulin C-terminal tail had more subtle effects on microtubule stability likely by modulating the interaction with kinesin-13. Overall, our study systematically assessed and compared several tubulin PTMs for their impacts on neuronal differentiation and regeneration and established an in vivo platform to test the function of tubulin PTMs in neurons.

Pubmed ID: 38949652

Antibodies used in this publication

None found

Associated grants

  • Agency: University of Hong Kong,
    Id: Seed fund 202011159053
  • Agency: Research Grants Council, University Grants Committee,
    Id: GRF 17107021
  • Agency: Research Grants Council, University Grants Committee,
    Id: ECS 27104219
  • Agency: Food and Health Bureau,
    Id: HMRF 07183186
  • Agency: University of Hong Kong,
    Id: Seed fund 201910159087
  • Agency: Research Grants Council, University Grants Committee,
    Id: C7064-22GF
  • Agency: Food and Health Bureau,
    Id: HMRF 09201426
  • Agency: National Natural Science Foundation of China,
    Id: Excellent Young Scientists Fund for Hong Kong and Macau 32122002
  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: Research Grants Council, University Grants Committee,
    Id: CRF C7026-20G
  • Agency: Research Grants Council, University Grants Committee,
    Id: GRF 17106322

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