Wang Haifeng, Brust-Mascher Ingrid, Scholey Jonathan M
Department of Molecular and Cell Biology, University of California at Davis, Davis, CA 95616.
Department of Molecular and Cell Biology, University of California at Davis, Davis, CA 95616
Mol Biol Cell. 2015 Apr 15;26(8):1452-62. doi: 10.1091/mbc.E14-12-1631. Epub 2015 Feb 18.
Chromosome segregation during anaphase depends on chromosome-to-pole motility and pole-to-pole separation. We propose that in Drosophila embryos, the latter process (anaphase B) depends on a persistent kinesin-5-generated interpolar (ip) microtubule (MT) sliding filament mechanism that "engages" to push apart the spindle poles when poleward flux is turned off. Here we investigated the contribution of the midzonal, antiparallel MT-cross-linking nonmotor MAP, Feo, to this "slide-and-flux-or-elongate" mechanism. Whereas Feo homologues in other systems enhance the midzone localization of the MT-MT cross-linking motors kinesin-4, -5 and -6, the midzone localization of these motors is respectively enhanced, reduced, and unaffected by Feo. Strikingly, kinesin-5 localizes all along ipMTs of the anaphase B spindle in the presence of Feo, including at the midzone, but the antibody-induced dissociation of Feo increases kinesin-5 association with the midzone, which becomes abnormally narrow, leading to impaired anaphase B and incomplete chromosome segregation. Thus, although Feo and kinesin-5 both preferentially cross-link MTs into antiparallel polarity patterns, kinesin-5 cannot substitute for loss of Feo function. We propose that Feo controls the organization, stability, and motor composition of antiparallel ipMTs at the midzone, thereby facilitating the kinesin-5-driven sliding filament mechanism underlying proper anaphase B spindle elongation and chromosome segregation.
后期的染色体分离取决于染色体向极的运动和极间的分离。我们提出,在果蝇胚胎中,后一过程(后期B)依赖于一种持续的由驱动蛋白-5产生的极间(ip)微管(MT)滑动丝机制,当向极流关闭时,该机制“启动”以推开纺锤体两极。在这里,我们研究了中间区域的、反平行MT交联非运动型微管相关蛋白(MAP)Feo对这种“滑动-流或伸长”机制的作用。在其他系统中,Feo同源物增强了MT-MT交联驱动蛋白4、5和6在中间区域的定位,而这些驱动蛋白在中间区域的定位分别因Feo而增强、减弱和不受影响。引人注目的是,在有Feo存在的情况下,驱动蛋白-5定位于后期B纺锤体的整个ipMT上,包括中间区域,但抗体诱导的Feo解离增加了驱动蛋白-5与中间区域的结合,中间区域变得异常狭窄,导致后期B受损和染色体分离不完全。因此,尽管Feo和驱动蛋白-5都优先将MT交联成反平行极性模式,但驱动蛋白-5不能替代Feo功能的丧失。我们提出,Feo控制中间区域反平行ipMT的组织、稳定性和驱动蛋白组成,从而促进驱动蛋白-5驱动的滑动丝机制,这是后期B纺锤体正常伸长和染色体分离的基础。