Force-transducing molecular ensembles at growing microtubule tips control mitotic spindle size

Abstract

AbstractMitotic spindle is a complex bipolar cellular structure that ensures chromosomes segregation between dividing cells. Correct spindle size is required for the accurate segregation and successful passing of genomes to the newly formed cells. The spindle size is believed to be controlled by mechanical forces generated by molecular motors and non-motor proteins acting in the spindle microtubule overlaps. However, how forces generated by individual proteins enable bipolar spindle organization is not well understood. Here, we developed tools to measure contributions of individual molecules to this force balance. We show that microtubule tip-trackers act synergetically at microtubule tips with minus-end directed motors to produce a system that can generate both pushing and pulling forces. We show that this system harnesses forces generated by growing tips of spindle microtubules and provides unique contribution to the force balance distinct from other force generators because it acts at microtubule tips rather than in microtubule overlaps. We show that this system alone can establish stable bipolar organization in vitro and in mitotic spindles in human cells. Our results pave the way for understanding how mechanical forces in spindles can be fine-tuned to control the fidelity of chromosome segregation.