Elevated polar ejection forces stabilize kinetochore–microtubule attachments

Abstract

Polar ejection forces, which push chromosomes away from spindle poles, modulate kinetochore–microtubule attachment stability.

Kinetochore Biorientation in Saccharomyces cerevisiae Requires a Tightly Folded Conformation of the Ndc80 Complex

“…We show that ndc80-121 cells contain aberrant kinetochore-microtubule attachments that are detached in an Ipl1-dependent manner. It is generally accepted that Ipl1 selectively detaches kinetochores that experience low levels of tension, which can include kinetochores that form either syntelic or weak microtubule attachments (Nicklas and Koch 1969;Tanaka et al 2002;Liu et al 2009;Cane et al 2013). We find that the ndc80-121 mutations do not weaken the microtubule attachment strength of the Ndc80 complex in vitro and that metaphase kinetochores in ndc80-121 cells can support tension across bioriented chromosomes at the restrictive temperature in vivo.…”

“…These erroneous kinetochore-microtubule attachments are detected and detached by the conserved Aurora B/Ipl1 kinase Tanaka et al 2002;Pinsky et al 2006). In the current prevailing model, Aurora B/Ipl1 corrects syntelic attachments by destabilizing linkages that are under low levels of tension (Nicklas and Koch 1969;Tanaka et al 2002;Liu et al 2009;Cane et al 2013). The Aurora B/Ipl1 error detection system is coupled to the spindle checkpoint, a separate surveillance system that delays anaphase until all kinetochores are attached to spindle microtubules (reviewed in Hauf 2013).…”

Dynein prevents erroneous kinetochore-microtubule attachments in mitosis

“…5,45,46 Importantly, chromosome ejection and attachment stabilization in the absence of Dynein were both repressed after simultaneous depletion of the 2 human chromokinesins (Kid and Kif4A), 5 in line with a recently reported role of PEFs in the stabilization of syntelic attachments in Drosophila S2 cells. 47 To dissect the functions of motor proteins at distinct chromosomal loci, as well as their respective contribution to chromosome movements, we used laser microsurgery to physically separate the chromosome arms from the kinetochorecontaining chromosome body. 5 To specifically investigate polar chromosomes we inhibited CENP-E prior to laser microsurgery, which locked a group of chromosomes at the spindle poles.…”

Building an integrated model of chromosome congression

“…Thus, the PEF is generated by the chromosome-arm-associated kinesins that walk towards the plus-ends of microtubules located at the spindle equator, therefore generating an AP force. As microtubule concentration is proportional to proximity to the pole, the strength of the PEF is inversely proportional to distance from a pole (Cane et al, 2013). Individually, depletion of Kid or Kif4a has only a minor effect on congression; however, co-depletion results in substantial alignment defects (Wandke et al, 2012), suggesting that these motors have independent and/or coordinated functions.…”