Luke-Glaser Sarah, Pintard Lionel, Tyers Mike, Peter Matthias
Institute of Biochemistry, HPM G8, ETH Hönggerberg, 8093 Zürich, Switzerland.
J Cell Sci. 2007 Sep 15;120(Pt 18):3179-87. doi: 10.1242/jcs.015883.
Members of the AAA-ATPase (ATPases associated with diverse cellular activities) family use the energy from ATP hydrolysis to disrupt protein complexes involved in many cellular processes. Here, we report that FIGL-1 (Fidgetin-like 1), the single Caenorhabditis elegans homolog of mammalian fidgetin and fidgetin-like 1 AAA-ATPases, controls progression through mitosis in the germ line and the early embryo. Loss of figl-1 function leads to the accumulation of mitotic nuclei in the proliferative zone of the germ line, resulting in sterility owing to depletion of germ cells. Like the AAA-ATPase MEI-1 (also known as katanin), FIGL-1 interacts with microtubules and with MEL-26, a specificity factor of CUL-3-based E3 ligases involved in targeting proteins for ubiquitin-dependent degradation by the 26S proteasome. In the germ line, FIGL-1 is enriched in nuclei of mitotic cells, but it disappears at the transition into meiosis. Conversely, MEL-26 expression is low in nuclei of the mitotic zone and induced during meiosis. FIGL-1 accumulates in the germ line and spreads to the meiotic zone after inactivation of mel-26 or cul-3 in vivo. We conclude that degradation of FIGL-1 by the CUL-3MEL-26 E3 ligase spatially restricts FIGL-1 function to mitotic cells, where it is required for correct progression through mitosis.
AAA-ATP酶(与多种细胞活动相关的ATP酶)家族成员利用ATP水解产生的能量来破坏参与许多细胞过程的蛋白质复合物。在此,我们报道,FIGL-1(类Fidgetin-1),即哺乳动物Fidgetin和类Fidgetin-1 AAA-ATP酶在秀丽隐杆线虫中的唯一同源物,控制生殖系和早期胚胎有丝分裂的进程。figl-1功能丧失导致生殖系增殖区有丝分裂细胞核积累,由于生殖细胞耗竭而导致不育。与AAA-ATP酶MEI-1(也称为katanin)一样,FIGL-1与微管以及MEL-26相互作用,MEL-26是基于CUL-3的E3连接酶的特异性因子,参与将蛋白质靶向26S蛋白酶体进行泛素依赖性降解。在生殖系中,FIGL-1在有丝分裂细胞的细胞核中富集,但在进入减数分裂时消失。相反,MEL-26在有丝分裂区细胞核中的表达较低,并在减数分裂期间被诱导。在体内mel-26或cul-3失活后,FIGL-1在生殖系中积累并扩散到减数分裂区。我们得出结论,CUL-3-MEL-26 E3连接酶对FIGL-1的降解在空间上将FIGL-1的功能限制在有丝分裂细胞中,在有丝分裂细胞中,它是有丝分裂正确进行所必需的。