Kinesin-5 acts as a brake in anaphase spindle elongation

Bipolar kinesin-5 motors, essential in diverse organisms, can generate positive sliding forces between overlapped interpolar microtubules to push mitotic spindle poles apart. BMK-1, the sole Caenorhabditis elegans kinesin-5, is not essential. We have determined, by tracking pole movements in bmk-1 mutant C. elegans embryos, that BMK-1 actually resists pole separation during anaphase. This provides in vivo evidence that kinesin-5, when challenged by fast pole separation forces, can serve as a rate-limiting brake for interpolar microtubule sliding. To organize and then accurately separate duplicated sets of chromosomes, eukaryotic cells construct a spindle. In many cell types, duplication of a centrosome creates two adjacent spindle poles that anchor microtubules by their minus ends to form aster-like radial arrays. Interpolar connections are formed between two asters when their microtubule plus ends associate laterally via crosslinking proteins to overlap in an antiparallel fashion [1]. A classic model posits that plusenddirected kinesin-5 type motors, which form bipolar heterotetramers, generate sliding forces between overlapped interpolar microtubules to push spindle poles apart [2,3]. Consistent with this, in vitro tests have shown that Xenopus kinesin5 (Eg5) can crosslink antiparallel microtubules and forcefully slide minus-ends away from one another [4]. This agrees with in vivo kinesin5 inhibition, which causes failure of pole separation, convergence of already separated poles, disruption of chromosome segregation and lethality in diverse organisms, from fungi to mammalian cells [5,6]. BMK-1, the sole C. elegans kinesin-5, provides a puzzling exception because inhibition 10 12 14 16 18 20 22 24 26 28