Microtubule poleward flux in human cells is driven by the coordinated action of four kinesins

• DOI: 10.1101/2020.06.16.155259
• Publication Date: 2020-06-17T13:17:07Z
• Authors: Yulia Steblyanko; Girish Rajendrapr...; Mariana Osswald; Susana Eibes; Stephan Geley; António J. Pereira; Helder Maiato; Marin Barisic
• Keywords: Prometaphase; Kinesin; Spindle pole body

Abstract Mitotic spindle microtubules (MTs) undergo continuous poleward flux, whose driving force and function in humans remain unclear. Here, we combined loss-of-function screenings with analysis of MT dynamics human cells to investigate the molecular mechanisms underlying MT-flux. We report that kinesin-7/CENP-E at kinetochores (KTs) is predominant driver MT-flux early prometaphase, while kinesin-4/KIF4A on chromosome arms facilitates during late prometaphase metaphase. show both these activities work coordination MT-crosslinking motors kinesin-5/EG5 kinesin-12/KIF15. Our data further indicate transmitted from non-KT MTs KT-MTs via MT-coupling by HSET NuMA. Moreover, found rate correlates size this correlation depends establishment stable end-on KT-MT attachments. Strikingly, revealed flux required counteract kinesin 13/MCAK-dependent MT-depolymerization regulate length. Thus, our study demonstrates driven coordinated action four kinesins, mitotic response MCAK-mediated MT-depolymerizing activity KTs.