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 Repjournal_title
EMBO reportsauthors
Tame MA,Raaijmakers JA,Afanasyev P,Medema RHdoi
10.15252/embr.201541143subject
Has Abstractpub_date
2016-03-01 00:00:00pages
317-25issue
3eissn
1469-221Xissn
1469-3178pii
embr.201541143journal_volume
17pub_type
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