Morelli Elena, Mastrodonato Valeria, Beznoussenko Galina V, Mironov Alexandre A, Tognon Emiliana, Vaccari Thomas
IFOM, The FIRC Institute of Molecular Oncology, Milan, Italy.
IFOM, The FIRC Institute of Molecular Oncology, Milan, Italy
EMBO J. 2016 Oct 17;35(20):2223-2237. doi: 10.15252/embj.201693991. Epub 2016 Sep 19.
The kinetochore is an essential structure that mediates accurate chromosome segregation in mitosis and meiosis. While many of the kinetochore components have been identified, the mechanisms of kinetochore assembly remain elusive. Here, we identify a novel role for Snap29, an unconventional SNARE, in promoting kinetochore assembly during mitosis in Drosophila and human cells. Snap29 localizes to the outer kinetochore and prevents chromosome mis-segregation and the formation of cells with fragmented nuclei. Snap29 promotes accurate chromosome segregation by mediating the recruitment of Knl1 at the kinetochore and ensuring stable microtubule attachments. Correct Knl1 localization to kinetochore requires human or Drosophila Snap29, and is prevented by a Snap29 point mutant that blocks Snap29 release from SNARE fusion complexes. Such mutant causes ectopic Knl1 recruitment to trafficking compartments. We propose that part of the outer kinetochore is functionally similar to membrane fusion interfaces.
动粒是一种重要结构，在有丝分裂和减数分裂中介导精确的染色体分离。虽然已经鉴定出许多动粒成分，但动粒组装的机制仍然难以捉摸。在这里，我们发现了一种非常规SNARE蛋白Snap29在促进果蝇和人类细胞有丝分裂期间动粒组装中的新作用。Snap29定位于外动粒，可防止染色体错误分离和形成核碎片化的细胞。Snap29通过介导Knl1在动粒处的募集并确保稳定的微管附着来促进精确的染色体分离。Knl1正确定位于动粒需要人类或果蝇的Snap29，而一种阻止Snap29从SNARE融合复合物中释放的Snap29点突变体则会阻止这种定位。这种突变体导致Knl1异位募集到运输小室。我们提出，外动粒的一部分在功能上类似于膜融合界面。
