Microtubule depolymerization at kinetochores restricts anaphase spindle elongation
摘要
Anaphase chromosome segregation depends on forces exerted by spindle microtubules. Current models propose two force-generating mechanisms: kinetochore–microtubule (kMT) depolymerization pulls chromosomes toward spindle poles (anaphase A), while antiparallel microtubule sliding in the central spindle further separates sister chromosomes by elongating the spindle (anaphase B). Experimental evidence in cells supports the sliding mechanism but contributions of the depolymerization mechanism remain unclear. We show that kMT depolymerization limits spindle elongation rather than moving chromosomes apart. We developed a chemical optogenetic approach to recruit microtubule depolymerases to kinetochores at anaphase onset, thereby increasing kMT depolymerization rates without perturbing earlier stages of mitosis. We find that increased depolymerization slows the velocity at which spindle poles move apart without changing kinetochore separation velocities. Our findings support a model in which kinetochores selectively couple to central spindle microtubules parallel to their kMTs, such that antiparallel sliding drives chromosome segregation while kMT depolymerization pulls poles inward.