In my many hours in a dark microscopy suite, I would stare slack-jawed at cells going through mitosis like a perv at a peep show. Beneath the grace of this serious cellular rite of passage is a massive amount of regulation, which just adds to the fascination so many biologists have for the event. Today’s image is from a paper that describes the generation and importance of forces that help align chromosomes on a metaphase plate.
During mitosis, chromosomes must align on the metaphase plate with attachments to opposite spindle poles. Only after this precise alignment can the cell begin a cascade of signals and checkpoints to trigger anaphase, which segregates sister chromatids into their eventual daughter cells. Chromosome alignment gets a hand from polar ejection forces (PEFs), which are forces generated by the microtubule-based motor kinesin found on chromosome arms. These chromokinsesins (kinesin-10 family members) are thought to walk chromosome arms away from spindle poles along microtubules, and are important for timely congression of chromosomes to the metaphase plate. A recent paper describes the relationship between PEFs and the stability of spindle-chromosome attachments. Cane and colleagues manipulated the levels of the fruit fly kinesin-10 protein NOD to similarly manipulate the tension and forces applied to chromosomes. When both kinetochores of a chromosome pair were incorrectly attached to the same spindle pole (called a syntelic attachment), NOD stabilized the attachments by preventing error correction by the protein Aurora B. From their results, Cane and colleagues show that PEFs regulate the stability of kinetochore attachment to spindle microtubules. In the time-lapse images above, NOD overexpression in a fruit fly cell caused an abnormal metaphase plate to form. Despite the syntelic attachments of many chromosomes, the cell still entered anaphase (AO), resulting in daughter cells with too many nuclei (far right image). NOD signal is red, microtubules are green.
BONUS!! Beautiful movies from the paper can be found here.
Cane, S., Ye, A., Luks-Morgan, S., & Maresca, T. (2013). Elevated polar ejection forces stabilize kinetochore-microtubule attachments originally published in the Journal of Cell Biology, 200 (2), 203-218 DOI: 10.1083/jcb.201211119