4.5 Article

Characterization of unconventional kinetochore kinases KKT10 and KKT19 in Trypanosoma brucei

期刊

JOURNAL OF CELL SCIENCE
卷 133, 期 8, 页码 -

出版社

COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.240978

关键词

Kinetoplastid kinetochore; Trypanosoma brucei; Kinase; KKT; Cell cycle

资金

  1. TOYOBO Biotechnology Foundation
  2. Wellcome Trust [210622/Z/18/Z]
  3. European Molecular Biology Organization
  4. University of Oxford

向作者/读者索取更多资源

The kinetochore is a macromolecular protein complex that drives chromosome segregation in eukaryotes. Unlike most eukaryotes that have canonical kinetochore proteins, evolutionarily divergent kinetoplastids, such as Trypanosoma brucei, have unconventional kinetochore proteins. T. brucei also lacks a canonical spindle checkpoint system, and it therefore remains unknown how mitotic progression is regulated in this organism. Here, we characterized, in the procyclic form of T. brucei, two paralogous kinetochore proteins with a CLK-like kinase domain, KKT10 and KKT19, which localize at kinetochores in metaphase but disappear at the onset of anaphase. We found that these proteins are functionally redundant. Double knockdown of KKT10 and KKT19 led to a significant delay in the metaphase to anaphase transition. We also found that phosphorylation of two kinetochore proteins, KKT4 and KKT7, depended on KKT10 and KKT19 in vivo. Finally, we showed that the N-terminal part of KKT7 directly interacts with KKT10 and that kinetochore localization of KKT10 depends not only on KKT7 but also on the KKT8 complex. Our results reveal that kinetochore localization of KKT10 and KKT19 is tightly controlled to regulate the metaphase to anaphase transition in T. brucei. This article has an associated First Person interview with the first author of the paper.

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