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 fine-tune Katanin level and activity to deliver the appropriate MT-severing activity during development.

中文翻译：

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微管切断 AAA+ 酶 Katanin 的磷酸化调节线虫胚胎发育

进化上保守的微管 (MT) 切断 AAA-ATP 酶 Katanin 正在成为 MT 动力学的关键调节因子。在秀丽隐杆线虫中，Katanin MT 切断活性对于减数分裂纺锤体组装至关重要，但对有丝分裂纺锤体有毒。在这里，我们分析了秀丽隐杆线虫中的Katanin动力学，并破译了Katanin磷酸化在调节其活性和稳定性中的作用。卵母细胞中剑肽含量丰富，减数分裂后其水平下降，但出乎意料的是，在整个胚胎发生过程中，剑肽存在很大一部分，在有丝分裂过程中，剑肽被动态招募到中心体和染色体。我们发现，在减数分裂过程中激活的小脑激酶 MBK-2 可在多个丝氨酸处磷酸化 Katanin。我们明确地证明，单个残基上的 Katanin 磷酸化对于减数分裂后的蛋白酶体降解来说是必要且充分的，而其他位点的磷酸化仅抑制 MT 刺激的 Katanin ATPase 活性。我们的研究结果表明，磷酸化和去磷酸化循环可微调 Katanin 水平和活性，以在发育过程中提供适当的 MT 切断活性。