Please use this identifier to cite or link to this item: https://biore.bio.bg.ac.rs/handle/123456789/2951
Title: The balance between KIFC3 and EG5 tetrameric kinesins controls the onset of mitotic spindle assembly
Authors: Hata, Shoji
Pastor Peidro, Ana
Panić, Marko 
Liu, Peng
Atorino, Enrico
Funaya, Charlotta
Jäkle, Ursula
Pereira, Gislene
Schiebel, Elmar
Issue Date: 2-Sep-2019
Rank: M21a
Journal: Nature Cell Biology
Abstract: 
© 2019, The Author(s), under exclusive licence to Springer Nature Limited. 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.
URI: https://biore.bio.bg.ac.rs/handle/123456789/2951
ISSN: 1465-7392
DOI: 10.1038/s41556-019-0382-6
Appears in Collections:Journal Article

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