4.7 Article

Phosphorylation of the microtubule-severing AAA plus enzyme Katanin regulates C. elegans embryo development

Journal

JOURNAL OF CELL BIOLOGY
Volume 219, Issue 6, Pages -

Publisher

ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201912037

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Funding

  1. National Institutes of Health Office of Research Infrastructure Programs [P40 OD010440]
  2. Ministry of Research
  3. Association pour la Recherche sur le Cancer Project Fellowship
  4. Agence Nationale de la Recherche, Universite de Paris excellency initiative (IdEx) [ANR-18-IDEX-0001]
  5. French Agence Nationale de la Recherche [ANR-17-CE13-0011-01/01]
  6. Ligue Contre le Cancer (Programme Equipes Labellisees)
  7. Agence Nationale de la Recherche, laboratory excellence (LabEx) Who Am I? [ANR-11-LABX-0071]
  8. Universite de Paris [IdEx ANR-18-IDEX-0001]
  9. Agence Nationale de la Recherche (ANR) [ANR-17-CE13-0011] Funding Source: Agence Nationale de la Recherche (ANR)

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The evolutionarily conserved microtubule (MT)-severing AAA-ATPase enzyme Katanin is emerging as a critical regulator of MT dynamics. In Caenorhabditis elegans, Katanin MT-severing activity is essential for meiotic spindle assembly but is toxic for the mitotic spindle. Here we analyzed Katanin dynamics in C. elegans and deciphered the role of Katanin phosphorylation in the regulation of its activity and stability. Katanin is abundant in oocytes, and its levels drop after meiosis, but unexpectedly, a significant fraction is present throughout embryogenesis, where it is dynamically recruited to the centrosomes and chromosomes during mitosis. We show that the minibrain kinase MBK-2, which is activated during meiosis, phosphorylates Katanin at multiple serines. We demonstrate unequivocally that Katanin phosphorylation at a single residue is necessary and sufficient to target Katanin for proteasomal degradation after meiosis, whereas phosphorylation at the other sites only inhibits Katanin ATPase activity stimulated by MTs. Our findings suggest that cycles of phosphorylation and dephosphorylation finetune Katanin level and activity to deliver the appropriate MT-severing activity during development.

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