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Interplay between stochastic enzyme activity and microtubule stability drives detyrosination enrichment on microtubule subsets.

Publication ,  Journal Article
Tang, Q; Sensale, S; Bond, C; Xing, J; Qiao, A; Hugelier, S; Arab, A; Arya, G; Lakadamyali, M
Published in: Current biology : CB
December 2023

Microtubules in cells consist of functionally diverse subpopulations carrying distinct post-translational modifications (PTMs). Akin to the histone code, the tubulin code regulates a myriad of microtubule functions, ranging from intracellular transport to chromosome segregation. However, how individual PTMs only occur on subsets of microtubules to contribute to microtubule specialization is not well understood. In particular, microtubule detyrosination, the removal of the C-terminal tyrosine on α-tubulin subunits, marks the stable population of microtubules and modifies how microtubules interact with other microtubule-associated proteins to regulate a wide range of cellular processes. Previously, we found that in certain cell types, only ∼30% of microtubules are highly enriched with the detyrosination mark and that detyrosination spans most of the length of a microtubule, often adjacent to a completely tyrosinated microtubule. How the activity of a cytosolic detyrosinase, vasohibin (VASH), leads to only a small subpopulation of highly detyrosinated microtubules is unclear. Here, using quantitative super-resolution microscopy, we visualized nascent microtubule detyrosination events in cells consisting of 1-3 detyrosinated α-tubulin subunits after nocodazole washout. Microtubule detyrosination accumulates slowly and in a dispersed pattern across the microtubule length. By visualizing single molecules of VASH in live cells, we found that VASH engages with microtubules stochastically on a short timescale, suggesting limited removal of tyrosine per interaction, consistent with the super-resolution results. Combining these quantitative imaging results with simulations incorporating parameters from our experiments, we provide evidence for a stochastic model for cells to establish a subset of detyrosinated microtubules via a detyrosination-stabilization feedback mechanism.

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Published In

Current biology : CB

DOI

EISSN

1879-0445

ISSN

0960-9822

Publication Date

December 2023

Volume

33

Issue

23

Start / End Page

5169 / 5184.e8

Related Subject Headings

  • Tyrosine
  • Tubulin
  • Protein Processing, Post-Translational
  • Microtubules
  • Microtubule-Associated Proteins
  • Developmental Biology
  • Cell Line
  • 52 Psychology
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
 

Citation

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Tang, Q., Sensale, S., Bond, C., Xing, J., Qiao, A., Hugelier, S., … Lakadamyali, M. (2023). Interplay between stochastic enzyme activity and microtubule stability drives detyrosination enrichment on microtubule subsets. Current Biology : CB, 33(23), 5169-5184.e8. https://doi.org/10.1016/j.cub.2023.10.068
Tang, Qing, Sebastian Sensale, Charles Bond, Jiazheng Xing, Andy Qiao, Siewert Hugelier, Arian Arab, Gaurav Arya, and Melike Lakadamyali. “Interplay between stochastic enzyme activity and microtubule stability drives detyrosination enrichment on microtubule subsets.Current Biology : CB 33, no. 23 (December 2023): 5169-5184.e8. https://doi.org/10.1016/j.cub.2023.10.068.
Tang Q, Sensale S, Bond C, Xing J, Qiao A, Hugelier S, et al. Interplay between stochastic enzyme activity and microtubule stability drives detyrosination enrichment on microtubule subsets. Current biology : CB. 2023 Dec;33(23):5169-5184.e8.
Tang, Qing, et al. “Interplay between stochastic enzyme activity and microtubule stability drives detyrosination enrichment on microtubule subsets.Current Biology : CB, vol. 33, no. 23, Dec. 2023, pp. 5169-5184.e8. Epmc, doi:10.1016/j.cub.2023.10.068.
Tang Q, Sensale S, Bond C, Xing J, Qiao A, Hugelier S, Arab A, Arya G, Lakadamyali M. Interplay between stochastic enzyme activity and microtubule stability drives detyrosination enrichment on microtubule subsets. Current biology : CB. 2023 Dec;33(23):5169-5184.e8.
Journal cover image

Published In

Current biology : CB

DOI

EISSN

1879-0445

ISSN

0960-9822

Publication Date

December 2023

Volume

33

Issue

23

Start / End Page

5169 / 5184.e8

Related Subject Headings

  • Tyrosine
  • Tubulin
  • Protein Processing, Post-Translational
  • Microtubules
  • Microtubule-Associated Proteins
  • Developmental Biology
  • Cell Line
  • 52 Psychology
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences