CRK2 controls cytoskeleton morphogenesis in Trypanosoma brucei by phosphorylating β-tubulin to regulate microtubule dynamics.

Microtubules constitute a vital part of the cytoskeleton in eukaryotes by mediating cell morphogenesis, cell motility, cell division, and intracellular transport. The cytoskeleton of the parasite Trypanosoma brucei contains an array of subpellicular microtubules with their plus-ends positioned towar...

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Main Authors: Kyu Joon Lee, Qing Zhou, Ziyin Li
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2023-03-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1011270
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author Kyu Joon Lee
Qing Zhou
Ziyin Li
author_facet Kyu Joon Lee
Qing Zhou
Ziyin Li
author_sort Kyu Joon Lee
collection DOAJ
description Microtubules constitute a vital part of the cytoskeleton in eukaryotes by mediating cell morphogenesis, cell motility, cell division, and intracellular transport. The cytoskeleton of the parasite Trypanosoma brucei contains an array of subpellicular microtubules with their plus-ends positioned toward the posterior cell tip, where extensive microtubule growth and cytoskeleton remodeling take place during early cell cycle stages. However, the control mechanism underlying microtubule dynamics at the posterior cell tip remains elusive. Here, we report that the S-phase cyclin-dependent kinase-cyclin complex CRK2-CYC13 in T. brucei regulates microtubule dynamics by phosphorylating β-tubulin on multiple evolutionarily conserved serine and threonine residues to inhibit its incorporation into cytoskeletal microtubules and promote its degradation in the cytosol. Consequently, knockdown of CRK2 or CYC13 causes excessive microtubule extension and loss of microtubule convergence at the posterior cell tip, leading to cytoskeleton elongation and branching. These findings uncover a control mechanism for cytoskeletal microtubule dynamics by which CRK2 phosphorylates β-tubulin and fine-tunes cellular β-tubulin protein abundance to restrict excess microtubule extension for the maintenance of cytoskeleton architecture.
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spelling doaj.art-d82c0adaf4014575b3067d48beb1018f2023-04-28T05:31:12ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-03-01193e101127010.1371/journal.ppat.1011270CRK2 controls cytoskeleton morphogenesis in Trypanosoma brucei by phosphorylating β-tubulin to regulate microtubule dynamics.Kyu Joon LeeQing ZhouZiyin LiMicrotubules constitute a vital part of the cytoskeleton in eukaryotes by mediating cell morphogenesis, cell motility, cell division, and intracellular transport. The cytoskeleton of the parasite Trypanosoma brucei contains an array of subpellicular microtubules with their plus-ends positioned toward the posterior cell tip, where extensive microtubule growth and cytoskeleton remodeling take place during early cell cycle stages. However, the control mechanism underlying microtubule dynamics at the posterior cell tip remains elusive. Here, we report that the S-phase cyclin-dependent kinase-cyclin complex CRK2-CYC13 in T. brucei regulates microtubule dynamics by phosphorylating β-tubulin on multiple evolutionarily conserved serine and threonine residues to inhibit its incorporation into cytoskeletal microtubules and promote its degradation in the cytosol. Consequently, knockdown of CRK2 or CYC13 causes excessive microtubule extension and loss of microtubule convergence at the posterior cell tip, leading to cytoskeleton elongation and branching. These findings uncover a control mechanism for cytoskeletal microtubule dynamics by which CRK2 phosphorylates β-tubulin and fine-tunes cellular β-tubulin protein abundance to restrict excess microtubule extension for the maintenance of cytoskeleton architecture.https://doi.org/10.1371/journal.ppat.1011270
spellingShingle Kyu Joon Lee
Qing Zhou
Ziyin Li
CRK2 controls cytoskeleton morphogenesis in Trypanosoma brucei by phosphorylating β-tubulin to regulate microtubule dynamics.
PLoS Pathogens
title CRK2 controls cytoskeleton morphogenesis in Trypanosoma brucei by phosphorylating β-tubulin to regulate microtubule dynamics.
title_full CRK2 controls cytoskeleton morphogenesis in Trypanosoma brucei by phosphorylating β-tubulin to regulate microtubule dynamics.
title_fullStr CRK2 controls cytoskeleton morphogenesis in Trypanosoma brucei by phosphorylating β-tubulin to regulate microtubule dynamics.
title_full_unstemmed CRK2 controls cytoskeleton morphogenesis in Trypanosoma brucei by phosphorylating β-tubulin to regulate microtubule dynamics.
title_short CRK2 controls cytoskeleton morphogenesis in Trypanosoma brucei by phosphorylating β-tubulin to regulate microtubule dynamics.
title_sort crk2 controls cytoskeleton morphogenesis in trypanosoma brucei by phosphorylating β tubulin to regulate microtubule dynamics
url https://doi.org/10.1371/journal.ppat.1011270
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