Dynamic localization of the chromosomal passenger complex in trypanosomes is controlled by the orphan kinesins KIN-A and KIN-B
The chromosomal passenger complex (CPC) is an important regulator of cell division, which shows dynamic subcellular localization throughout mitosis, including kinetochores and the spindle midzone. In traditional model eukaryotes such as yeasts and humans, the CPC consists of the catalytic subunit Au...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2024-04-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/93522 |
| _version_ | 1797221101391052800 |
|---|---|
| author | Daniel Ballmer Bungo Akiyoshi |
| author_facet | Daniel Ballmer Bungo Akiyoshi |
| author_sort | Daniel Ballmer |
| collection | DOAJ |
| description | The chromosomal passenger complex (CPC) is an important regulator of cell division, which shows dynamic subcellular localization throughout mitosis, including kinetochores and the spindle midzone. In traditional model eukaryotes such as yeasts and humans, the CPC consists of the catalytic subunit Aurora B kinase, its activator INCENP, and the localization module proteins Borealin and Survivin. Intriguingly, Aurora B and INCENP as well as their localization pattern are conserved in kinetoplastids, an evolutionarily divergent group of eukaryotes that possess unique kinetochore proteins and lack homologs of Borealin or Survivin. It is not understood how the kinetoplastid CPC assembles nor how it is targeted to its subcellular destinations during the cell cycle. Here, we identify two orphan kinesins, KIN-A and KIN-B, as bona fide CPC proteins in Trypanosoma brucei, the kinetoplastid parasite that causes African sleeping sickness. KIN-A and KIN-B form a scaffold for the assembly of the remaining CPC subunits. We show that the C-terminal unstructured tail of KIN-A interacts with the KKT8 complex at kinetochores, while its N-terminal motor domain promotes CPC translocation to spindle microtubules. Thus, the KIN-A:KIN-B complex constitutes a unique ‘two-in-one’ CPC localization module, which directs the CPC to kinetochores from S phase until metaphase and to the central spindle in anaphase. Our findings highlight the evolutionary diversity of CPC proteins and raise the possibility that kinesins may have served as the original transport vehicles for Aurora kinases in early eukaryotes. |
| first_indexed | 2024-04-24T13:00:05Z |
| format | Article |
| id | doaj.art-c6c41d08bcf04d179bedbdbd44fa8c16 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-24T13:00:05Z |
| publishDate | 2024-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c6c41d08bcf04d179bedbdbd44fa8c162024-04-05T14:28:29ZengeLife Sciences Publications LtdeLife2050-084X2024-04-011310.7554/eLife.93522Dynamic localization of the chromosomal passenger complex in trypanosomes is controlled by the orphan kinesins KIN-A and KIN-BDaniel Ballmer0https://orcid.org/0000-0002-1966-0960Bungo Akiyoshi1https://orcid.org/0000-0001-6010-394XDepartment of Biochemistry, University of Oxford, Oxford, United Kingdom; The Wellcome Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, Edinburgh, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United Kingdom; The Wellcome Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, Edinburgh, United KingdomThe chromosomal passenger complex (CPC) is an important regulator of cell division, which shows dynamic subcellular localization throughout mitosis, including kinetochores and the spindle midzone. In traditional model eukaryotes such as yeasts and humans, the CPC consists of the catalytic subunit Aurora B kinase, its activator INCENP, and the localization module proteins Borealin and Survivin. Intriguingly, Aurora B and INCENP as well as their localization pattern are conserved in kinetoplastids, an evolutionarily divergent group of eukaryotes that possess unique kinetochore proteins and lack homologs of Borealin or Survivin. It is not understood how the kinetoplastid CPC assembles nor how it is targeted to its subcellular destinations during the cell cycle. Here, we identify two orphan kinesins, KIN-A and KIN-B, as bona fide CPC proteins in Trypanosoma brucei, the kinetoplastid parasite that causes African sleeping sickness. KIN-A and KIN-B form a scaffold for the assembly of the remaining CPC subunits. We show that the C-terminal unstructured tail of KIN-A interacts with the KKT8 complex at kinetochores, while its N-terminal motor domain promotes CPC translocation to spindle microtubules. Thus, the KIN-A:KIN-B complex constitutes a unique ‘two-in-one’ CPC localization module, which directs the CPC to kinetochores from S phase until metaphase and to the central spindle in anaphase. Our findings highlight the evolutionary diversity of CPC proteins and raise the possibility that kinesins may have served as the original transport vehicles for Aurora kinases in early eukaryotes.https://elifesciences.org/articles/93522Trypanosoma bruceikinetoplastidkinetochorechromosomal passenger complexkinesin |
| spellingShingle | Daniel Ballmer Bungo Akiyoshi Dynamic localization of the chromosomal passenger complex in trypanosomes is controlled by the orphan kinesins KIN-A and KIN-B eLife Trypanosoma brucei kinetoplastid kinetochore chromosomal passenger complex kinesin |
| title | Dynamic localization of the chromosomal passenger complex in trypanosomes is controlled by the orphan kinesins KIN-A and KIN-B |
| title_full | Dynamic localization of the chromosomal passenger complex in trypanosomes is controlled by the orphan kinesins KIN-A and KIN-B |
| title_fullStr | Dynamic localization of the chromosomal passenger complex in trypanosomes is controlled by the orphan kinesins KIN-A and KIN-B |
| title_full_unstemmed | Dynamic localization of the chromosomal passenger complex in trypanosomes is controlled by the orphan kinesins KIN-A and KIN-B |
| title_short | Dynamic localization of the chromosomal passenger complex in trypanosomes is controlled by the orphan kinesins KIN-A and KIN-B |
| title_sort | dynamic localization of the chromosomal passenger complex in trypanosomes is controlled by the orphan kinesins kin a and kin b |
| topic | Trypanosoma brucei kinetoplastid kinetochore chromosomal passenger complex kinesin |
| url | https://elifesciences.org/articles/93522 |
| work_keys_str_mv | AT danielballmer dynamiclocalizationofthechromosomalpassengercomplexintrypanosomesiscontrolledbytheorphankinesinskinaandkinb AT bungoakiyoshi dynamiclocalizationofthechromosomalpassengercomplexintrypanosomesiscontrolledbytheorphankinesinskinaandkinb |