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The balance between KIFC3 and EG5 tetrameric kinesins controls the onset of mitotic spindle assembly

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...

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Main Authors: Hata, Shoji (Author) , Pastor Peidro, Ana (Author) , Panić, Marko (Author) , Liu, Peng (Author) , Atorino, Enrico (Author) , Jäkle, Ursula (Author) , Pereira, Gislene (Author) , Schiebel, Elmar (Author)
Format: Article (Journal)
Language:English
Published: 02 September 2019
In: Nature cell biology
Year: 2019, Volume: 21, Issue: 9, Pages: 1138-1151
ISSN:1476-4679
DOI:10.1038/s41556-019-0382-6
Online Access:Verlag, Volltext: https://doi.org/10.1038/s41556-019-0382-6
Verlag: https://www.nature.com/articles/s41556-019-0382-6
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Author Notes:Shoji Hata, Ana Pastor Peidro, Marko Panic, Peng Liu, Enrico Atorino, Charlotta Funaya, Ursula Jäkle, Gislene Pereira and Elmar Schiebel
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Summary: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.
Item Description:Gesehen am 09.10.2019
Physical Description:Online Resource
ISSN:1476-4679
DOI:10.1038/s41556-019-0382-6

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