Chromosome misalignments induce spindle-positioning defects.

Abstract:

:Cortical pulling forces on astral microtubules are essential to position the spindle. These forces are generated by cortical dynein, a minus-end directed motor. Previously, another dynein regulator termed Spindly was proposed to regulate dynein-dependent spindle positioning. However, the mechanism of how Spindly regulates spindle positioning has remained elusive. Here, we find that the misalignment of chromosomes caused by Spindly depletion is directly provoking spindle misorientation. Chromosome misalignments induced by CLIP-170 or CENP-E depletion or by noscapine treatment are similarly accompanied by severe spindle-positioning defects. We find that cortical LGN is actively displaced from the cortex when misaligned chromosomes are in close proximity. Preventing the KT recruitment of Plk1 by the depletion of PBIP1 rescues cortical LGN enrichment near misaligned chromosomes and re-establishes proper spindle orientation. Hence, KT-enriched Plk1 is responsible for the negative regulation of cortical LGN localization. In summary, we uncovered a compelling molecular link between chromosome alignment and spindle orientation defects, both of which are implicated in tumorigenesis.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Tame MA,Raaijmakers JA,Afanasyev P,Medema RH

doi

10.15252/embr.201541143

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

317-25

issue

3

eissn

1469-221X

issn

1469-3178

pii

embr.201541143

journal_volume

17

pub_type

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