Institut Jacques Monod, Centre National de la Recherche Scientifique, UMR 7592, University of Paris Diderot, F-75205 Paris, France.
J Cell Biol. 2013 Aug 5;202(3):431-9. doi: 10.1083/jcb.201304174.
Katanin is an evolutionarily conserved microtubule (MT)-severing complex implicated in multiple aspects of MT dynamics. In Caenorhabditis elegans, the katanin homologue MEI-1 is required for meiosis, but must be inactivated before mitosis. Here we show that PPFR-1, a regulatory subunit of a trimeric protein phosphatase 4 complex, enhanced katanin MT-severing activity during C. elegans meiosis. Loss of ppfr-1, similarly to the inactivation of MT severing, caused a specific defect in meiosis II spindle disassembly. We show that a fraction of PPFR-1 was degraded after meiosis, contributing to katanin inactivation. PPFR-1 interacted with MEL-26, the substrate recognition subunit of the CUL-3 RING E3 ligase (CRL3(MEL-26)), which also targeted MEI-1 for post-meiotic degradation. Reversible protein phosphorylation of MEI-1 may ensure temporal activation of the katanin complex during meiosis, whereas CRL3(MEL-26)-mediated degradation of both MEI-1 and its activator PPFR-1 ensure efficient katanin inactivation in the transition to mitosis.
katanin 是一种进化上保守的微管 (MT)-切断复合物，涉及 MT 动力学的多个方面。在秀丽隐杆线虫中，katanin 同源物 MEI-1 是减数分裂所必需的，但必须在有丝分裂之前失活。在这里，我们表明，PPFR-1，一种三聚体蛋白磷酸酶 4 复合物的调节亚基，增强了秀丽隐杆线虫减数分裂过程中的 katanin MT 切断活性。ppfr-1 的缺失，类似于 MT 切断的失活，导致减数分裂 II 纺锤体解体的特定缺陷。我们表明，PPFR-1 的一部分在减数分裂后被降解，有助于 katanin 的失活。PPFR-1 与 MEL-26 相互作用，MEL-26 是 CUL-3 RING E3 连接酶 (CRL3(MEL-26)) 的底物识别亚基，该酶也将 MEI-1 靶向减数分裂后降解。MEI-1 的可逆蛋白磷酸化可能确保了 katanin 复合物在减数分裂过程中的时间激活，而 CRL3(MEL-26)介导的 MEI-1 及其激活剂 PPFR-1 的降解确保了在向有丝分裂过渡时 katanin 的有效失活。
