Coordinated control of both microtubule ends regulates mitotic spindle length

Abstract

Abstract The mitotic spindle is a biomechanical structure whose length must be precisely controlled to ensure faithful chromosome segregation. The treadmilling of microtubules towards spindle poles, termed poleward flux, is involved in spindle length control. However, poleward flux velocity has been shown to be both inversely and directly proportional to spindle length, a contradiction that remains unexplained by current mechanisms. Here we introduce a model which demonstrates that length-dependent regulation at both microtubule ends allows plus- and minus-end dynamics to synchronize with one another, enabling pathways of poleward-flux-based spindle length control which rectify previous results. Moreover, our model predicts that spindle length and poleward flux velocity can vary independently via simultaneous perturbations at both microtubule ends, which we validate with protein depletion experiments in human cells. Finally, we provide experimental evidence for length-dependent accumulation of proteins at microtubule minus-ends. Our results thus resolve a longstanding paradox and provide mechanistic insight into the reciprocal control of spindle length and poleward flux.