Discovery of unconventional kinetochores in kinetoplastids

The kinetochore is the macromolecular protein complex that drives chromosome segregation in eukaryotes. Although it was widely assumed that the core kinetochore consists of proteins that are common to all eukaryotes, we found that the evolutionarily distant kinetoplastids build kinetochores using a novel set of proteins.

HFSP Long-Term Fellow Bungo Akiyoshi and Program Grant holder Keith Gull and colleagues
authored on Thu, 24 April 2014

Faithful transmission of genetic material requires that the kinetochore complex interacts with dynamic spindle microtubules during mitosis and meiosis. Spindle microtubules that consist of tubulin subunits are ubiquitously used in all eukaryotes studied thus far. By contrast, it was not clear if all eukaryotes build kinetochores using similar kinetochore proteins because no conventional kinetochore components have been identified in any kinetoplastid genome.

Figure: Trypanosome cell with a YFP-tagged kinetochore protein (green) and DNA stained with DAPI (purple)

Using a localization-based screen and proteomics approach, we identified 19 kinetochore proteins in an experimentally tractable kinetoplastid parasite, Trypanosoma brucei. Although the majority is conserved among kinetoplastids, none of them has detectable homology to kinetochore proteins found in other eukaryotes, suggesting that kinetoplastids build kinetochores using a distinct set of proteins. Understanding how these proteins carry out kinetochore functions (e.g. interact with spindle microtubules and centromere DNA) should lead to a better understanding of the chromosome segregation machinery in kinetoplastids as well as other eukaryotes. Interestingly, this finding supports the controversial hypothesis that kinetoplastids represent the earliest-branching eukaryotes. Furthermore, these unconventional kinetochore proteins, being distinct from human kinetochore proteins, may represent an attractive drug target for kinetoplastid diseases, such as sleeping sickness (caused by Trypanosoma brucei), Chagas disease (caused by Trypanosoma cruzi) and leishmaniasis (caused by Leishmania species).

Reference

Discovery of unconventional kinetochores in kinetoplastids. Akiyoshi B, Gull K (2014) Cell 156:1247–1258.

Pubmed link

Link to Cell article (open access)

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