Individual kinetochore-fibers locally dissipate force to maintain robust mammalian spindle structure.
J Cell Biol
; 219(8)2020 08 03.
Article
in En
| MEDLINE
| ID: mdl-32435797
ABSTRACT
At cell division, the mammalian kinetochore binds many spindle microtubules that make up the kinetochore-fiber. To segregate chromosomes, the kinetochore-fiber must be dynamic and generate and respond to force. Yet, how it remodels under force remains poorly understood. Kinetochore-fibers cannot be reconstituted in vitro, and exerting controlled forces in vivo remains challenging. Here, we use microneedles to pull on mammalian kinetochore-fibers and probe how sustained force regulates their dynamics and structure. We show that force lengthens kinetochore-fibers by persistently favoring plus-end polymerization, not by increasing polymerization rate. We demonstrate that force suppresses depolymerization at both plus and minus ends, rather than sliding microtubules within the kinetochore-fiber. Finally, we observe that kinetochore-fibers break but do not detach from kinetochores or poles. Together, this work suggests an engineering principle for spindle structural homeostasis different physical mechanisms of local force dissipation by the k-fiber limit force transmission to preserve robust spindle structure. These findings may inform how other dynamic, force-generating cellular machines achieve mechanical robustness.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Kinetochores
/
Chromosome Segregation
/
Mechanotransduction, Cellular
/
Epithelial Cells
/
Kidney
/
Spindle Apparatus
Limits:
Animals
Language:
En
Journal:
J Cell Biol
Year:
2020
Document type:
Article
Affiliation country: