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Microtubule poleward flux in human cells is driven by the coordinated action of four kinesins
Author(s) -
Steblyanko Yulia,
Rajendraprasad Girish,
Osswald Mariana,
Eibes Susana,
Jacome Ariana,
Geley Stephan,
Pereira António J,
Maiato Helder,
Barisic Marin
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020105432
Subject(s) - prometaphase , kinesin , microtubule , biology , kinetochore , mitosis , microbiology and biotechnology , metaphase , spindle pole body , flux (metallurgy) , spindle apparatus , chromosome segregation , biophysics , cell division , genetics , chromosome , cell , chemistry , organic chemistry , gene
Mitotic spindle microtubules ( MT s) 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 in human cells to investigate the molecular mechanisms underlying MT ‐flux. We report that kinesin‐7/ CENP ‐E at kinetochores ( KT s) is the predominant driver of MT ‐flux in early prometaphase, while kinesin‐4/ KIF 4A on chromosome arms facilitates MT ‐flux during late prometaphase and metaphase. Both these activities work in coordination with kinesin‐5/ EG 5 and kinesin‐12/ KIF 15, and our data suggest that the MT ‐flux driving force is transmitted from non‐ KT ‐ MT s to KT ‐ MT s by the MT couplers HSET and Nu MA . Additionally, we found that the MT ‐flux rate correlates with spindle length, and this correlation depends on the establishment of stable end‐on KT ‐ MT attachments. Strikingly, we find that MT ‐flux is required to regulate spindle length by counteracting kinesin 13/ MCAK ‐dependent MT ‐depolymerization. Thus, our study unveils the long‐sought mechanism of MT ‐flux in human cells as relying on the coordinated action of four kinesins to compensate for MT ‐depolymerization and regulate spindle length.