Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 293, Issue 26, Pages 10275-10286Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.RA118.003113
Keywords
cell cycle; cell division; cytokinesis; parasite; Trypanosoma brucei; Aurora B kinase; kinetoplastid; polo-like kinase; sleeping sickness; trypanosomiasis; CIF1; CIF2; CIF3
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Funding
- National Institutes of Health [AI101437, AI118736]
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Cytokinesis, the terminal step in cell division, in the protist human pathogen Trypanosoma brucei occurs along the longitudinal axis from the anterior tip of the new flagellum attachment zone (FAZ) toward the posterior cell tip. This process is regulated by a signaling cascade composed of the Polo-like kinase homolog TbPLK, the Aurora B kinase homolog TbAUK1, and the trypanosome-specific CIF1-CIF2 protein complex. However, the regulatory mechanism and the signaling pathway for this unusual mode of cytokinesis remain poorly understood. Here, we report another trypanosome-specific protein assembly, the CIF1-CIF3 complex, and its essential role in cytokinesis initiation. Through biochemical and genetic approaches, we demonstrate that CIF3 interacts with CIF1 in a TbPLK-dependent manner and maintains CIF1 localization at the new FAZ tip. Conversely, CIF1 maintains CIF3 stability at the new FAZ tip. We further show that TbPLK is required for CIF3 localization and that CIF3 is necessary for targeting TbAUK1 to the new FAZ tip during anaphase. These results suggest that two trypanosome-specific CIF1-containing protein complexes cooperate with the evolutionarily conserved Polo-like kinase and Aurora B kinase to promote cytokinesis in T. brucei.
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