Aurora B controls anaphase onset and error-free chromosomes segregation in trypanosomes

Ballmer, D., Lou, H.J., Ishii, M., Turk, B.E., and Akiyoshi, B

By Jenna Hare

Cell division is a vital process for all living organisms and involves a parental cell splitting into two identical daughter cells. The process of cell division is part of a larger ‘cell cycle’, which also includes cell growth and DNA replication. During mitosis, duplicated chromosomes are pulled apart into two daughter cells by attaching to spindle microtubules. The kinetochore refers to the protein structure that provides a linkage between chromosomes and spindle microtubules. The kinetochore-microtubule interface is carefully monitored by various regulatory proteins, including the Aurora B kinase: the catalytic subunit of the chromosomal passenger complex. Here, the Akiyoshi lab has researched the function of Aurora B in Trypanosome brucei, a protozoan parasite that has a unique set of kinetochore proteins.

They explored the function of Aurora B by inhibiting its activity using an analogue-sensitive approach. They found multiple defects when they inhibited Aurora B. Firstly, the cell cycle could not progress from metaphase to anaphase and secondly microtubules were less stable. They also used electron microscopy techniques and found reduced tension across the inter-sister kinetochore axis when Aurora B is inhibited. This means that trypanosome cells need Aurora B activity to ensure stable microtubule attachment. They next looked for substrates of Aurora B using recombinant proteins. They found that Aurora B phosphorylated multiple kinetochore components including a divergent spindle checkpoint protein KKT14. With mass spectrometry, they found specific sites of KKT14 that are phosphorylated by Aurora B and revealed a mechanism for how Aurora B promotes anaphase entry.

Overall, researchers from the Akiyoshi lab have further explored the function of Aurora B in cell cycle mechanisms and its regulation in trypanosomes that are evolutionarily divergent from traditional model eukaryotes such as yeast or human.