The Francis Crick Institute, London, United Kingdom.
King's College London, London, UK.
Nat Commun. 2024 Nov 14;15(1):9865. doi: 10.1038/s41467-024-54123-2.
Correct mitotic spindle size is required for accurate chromosome segregation during cell division. It is controlled by mechanical forces generated by molecular motors and non-motor proteins acting on spindle microtubules. However, how forces generated by individual proteins enable bipolar spindle organization is not well understood. Here, we develop tools to measure contributions of individual molecules to this force balance. We show that microtubule plus-end binding proteins act at microtubule tips synergistically with minus-end directed motors to produce a system that can generate both pushing and pulling forces. To generate pushing force, the system harnesses forces generated by the growing tips of microtubules providing unique contribution to the force balance distinct from all other motors that act in the mitotic spindle. Our results reveal that microtubules are essential force generators for establishing spindle size and pave the way for understanding how mechanical forces can be fine-tuned to control the fidelity of chromosome segregation.
正确的有丝分裂纺锤体大小对于细胞分裂过程中染色体的准确分离是必需的。它由作用于纺锤体微管的分子马达和非马达蛋白产生的机械力控制。然而,单个蛋白质产生的力如何使双极纺锤体组织化尚不清楚。在这里,我们开发了测量单个分子对这种力平衡贡献的工具。我们表明,微管正极结合蛋白与负向定向马达一起在微管尖端协同作用,产生一个既能产生推和拉两种力的系统。为了产生推力,该系统利用微管生长尖端产生的力,为力平衡提供独特的贡献,这与在有丝分裂纺锤体中作用的所有其他马达都不同。我们的结果表明,微管是建立纺锤体大小的必需力发生器,并为理解机械力如何被精细调节以控制染色体分离的保真度铺平了道路。