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doi: 10.1038/ncb2423
pmid: 22307330
Loss of spindle-pole integrity during mitosis leads to multipolarity independent of centrosome amplification. Multipolar-spindle conformation favours incorrect kinetochore-microtubule attachments, compromising faithful chromosome segregation and daughter-cell viability. Spindle-pole organization influences and is influenced by kinetochore activity, but the molecular nature behind this critical force balance is unknown. CLASPs are microtubule-, kinetochore- and centrosome-associated proteins whose functional perturbation leads to three main spindle abnormalities: monopolarity, short spindles and multipolarity. The first two reflect a role at the kinetochore-microtubule interface through interaction with specific kinetochore partners, but how CLASPs prevent spindle multipolarity remains unclear. Here we found that human CLASPs ensure spindle-pole integrity after bipolarization in response to CENP-E- and Kid-mediated forces from misaligned chromosomes. This function is independent of end-on kinetochore-microtubule attachments and involves the recruitment of ninein to residual pericentriolar satellites. Distinctively, multipolarity arising through this mechanism often persists through anaphase. We propose that CLASPs and ninein confer spindle-pole resistance to traction forces exerted during chromosome congression, thereby preventing irreversible spindle multipolarity and aneuploidy.
Cytochalasin D, Metaphase/physiology, Chromosomal Proteins, Non-Histone, Blotting, Western, Green Fluorescent Proteins, Mitosis, Chromosomal Proteins, Non-Histone/metabolism/physiology, Spindle Apparatus, Models, Biological, Time-Lapse Imaging, Green Fluorescent Proteins/genetics/metabolism, Cell Line, Tumor, Chromosome Segregation, Humans, Kinetochores, Metaphase, Centrosome, Mitosis/physiology, Microscopy, Fluorescence, Centrosome/metabolism/physiology, Cytochalasin D/pharmacology, RNA Interference, Microtubule-Associated Proteins/genetics/metabolism/physiology, Mitotic Spindle Apparatus/drug effects/metabolism/physiology, Chromosome Segregation/physiology, Microtubule-Associated Proteins, Kinetochores/metabolism/physiology, HeLa Cells
Cytochalasin D, Metaphase/physiology, Chromosomal Proteins, Non-Histone, Blotting, Western, Green Fluorescent Proteins, Mitosis, Chromosomal Proteins, Non-Histone/metabolism/physiology, Spindle Apparatus, Models, Biological, Time-Lapse Imaging, Green Fluorescent Proteins/genetics/metabolism, Cell Line, Tumor, Chromosome Segregation, Humans, Kinetochores, Metaphase, Centrosome, Mitosis/physiology, Microscopy, Fluorescence, Centrosome/metabolism/physiology, Cytochalasin D/pharmacology, RNA Interference, Microtubule-Associated Proteins/genetics/metabolism/physiology, Mitotic Spindle Apparatus/drug effects/metabolism/physiology, Chromosome Segregation/physiology, Microtubule-Associated Proteins, Kinetochores/metabolism/physiology, HeLa Cells
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | 91 | |
popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network. | Top 10% | |
influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Top 10% | |
impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Top 1% |