2026-03-25 ロックフェラー大学
微小管に結合したNdc80複合体の構造。Ndc80複合体は、動原体における主要な微小管結合モジュールである。緑色：α-チューブリン、水色：β-チューブリン、濃青色：HEC1（Ndc80複合体のαサブユニット）、黄色：NUF2（Ndc80複合体のαサブユニット）。（画像提供：船引研究室）
＜関連情報＞
- https://www.rockefeller.edu/news/39227-microtubules-discovered-to-play-an-active-role-in-correctly-distributing-chromosomes-during-cell-division/
- https://www.science.org/doi/10.1126/sciadv.aea2112
微小管は、正確な染色体分離のためにオーロラB基質の形状を誘導する Microtubules guide Aurora B substrate geometries for accurate chromosome segregation
Yiming Niu, Keith F. DeLuca, Randall H. Owen, Hide A. Konishi, […] , and Hironori Funabiki
Science Advances Published:25 Mar 2026
DOI:https://doi.org/10.1126/sciadv.aea2112
Abstract
Accurate chromosome segregation requires differential regulation of microtubule-binding substrates by Aurora B, the kinase subunit of the chromosomal passenger complex (CPC). How microtubules simultaneously up- and down-regulate Aurora B phosphorylation remains unclear. Devising a new cryo–electron microscopy workflow, we determined microtubule-bound structures of the CPC and key Aurora B substrates that resolve their phosphorylation sites, finding that microtubules can promote or restrict Aurora B–mediated phosphorylation depending upon binding geometry. The kinetochore Ndc80 complex oligomerizes on microtubules through multivalent interactions including its kinase recognition sites, sterically restricting kinase access to counteract phosphorylation-induced detachment. Attenuating this oligomerization compromised stable kinetochore-microtubule attachments and causes chromosome mis-segregation. Conversely, Aurora B recognition sites of the microtubule-depolymerase mitotic centromere–associated kinesin (MCAK) remain accessible on microtubules, explaining how microtubule-bound CPC can promote MCAK phosphorylation and inactivation. We propose that microtubule-guided substrate remodeling can serve as a general mechanism for controlling Aurora B–mediated phosphorylation during mitosis, which can coordinate diverse processes underlying faithful chromosome segregation.
