The balance between KIFC3 and EG5 tetrameric kinesins controls the onset of mitotic spindle assembly
| العنوان: | The balance between KIFC3 and EG5 tetrameric kinesins controls the onset of mitotic spindle assembly |
|---|---|
| المؤلفون: | Enrico Atorino, Gislene Pereira, Shoji Hata, Ursula Jäkle, Charlotta Funaya, Ana Pastor Peidro, Peng Liu, Marko Panic, Elmar Schiebel |
| المصدر: | Nature Cell Biology. 21:1138-1151 |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0303 health sciences, Chemistry, Cell Biology, Cell biology, 03 medical and health sciences, 0302 clinical medicine, Centrosome, Microtubule, 030220 oncology & carcinogenesis, Kinesin, Centrosome separation, Mitosis, Linker, Multipolar spindles, 030304 developmental biology, Homotetramer |
| الوصف: | One of the first steps in mitotic spindle assembly is the dissolution of the centrosome linker followed by centrosome separation driven by EG5, a tetrameric plus-end-directed member of the kinesin-5 family. However, even in the absence of the centrosome linker, the two centrosomes are kept together by an ill-defined microtubule-dependent mechanism. Here we show that KIFC3, a minus-end-directed kinesin-14, provides microtubule-based centrosome cohesion. KIFC3 forms a homotetramer that pulls the two centrosomes together via a specific microtubule network. At mitotic onset, KIFC3 activity becomes the main driving force of centrosome cohesion to prevent premature spindle formation after linker dissolution as it counteracts the increasing EG5-driven pushing forces. KIFC3 is eventually inactivated by NEver in mitosis-related Kinase 2 (NEK2) to enable EG5-driven bipolar spindle assembly. We further show that persistent centrosome cohesion in mitosis leads to chromosome mis-segregation. Our findings reveal a mechanism of spindle assembly that is evolutionary conserved from yeast to humans. |
| تدمد: | 1476-4679 1465-7392 |
| DOI: | 10.1038/s41556-019-0382-6 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::c17cf878f75f98b25fc2e4bdc04490ed https://doi.org/10.1038/s41556-019-0382-6 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi...........c17cf878f75f98b25fc2e4bdc04490ed |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14764679 14657392 |
|---|---|
| DOI: | 10.1038/s41556-019-0382-6 |