The trypanosome-specific proteins FPRC and CIF4 regulate cytokinesis initiation by recruiting CIF1 to the cytokinesis initiation site [Microbiology]

September 20th, 2019 by Huiqing Hu, Tai An, Yasuhiro Kurasawa, Qing Zhou, Ziyin Li

The evolutionarily early divergent human parasite Trypanosoma brucei proliferates through binary cell fission in both its tsetse fly vector and mammalian host. The parasite divides uni-directionally along the longitudinal cell axis from the anterior cell tip toward the posterior cell tip through a mechanism distinct from that in the cells of its human host. Initiation of cytokinesis in T. brucei is regulated by two evolutionarily conserved protein kinases, the Polo-like kinase TbPLK and the Aurora B kinase TbAUK1, and a cohort of trypanosome-specific proteins, including three cytokinesis initiation factors CIF1, CIF2, and CIF3. Here, using RNA interference, in situ epitope tagging of proteins, GST pull-down and co-immunoprecipitation assays, and immunofluorescence and scanning EM microscopy analyses, we report the identification and functional characterization of two trypanosome-specific proteins, FPRC and CIF4. We found that the two proteins co-localize to the distal tips of the new and the old flagellum attachment zones, and are required for cytokinesis initiation. Knockdown of FPRC or CIF4 each disrupted the localization of CIF1, suggesting that they function upstream of CIF1. Moreover, depletion of CIF4 abolished FPRC localization, indicating that CIF4 acts upstream of FPRC. Together, these results identify two new cytokinesis regulators in T. brucei and integrate them into the CIF1-mediated cytokinesis regulatory pathway. These findings highlight the existence of a cytokinesis pathway in T. brucei that is different from that of its mammalian host and therefore suggest that cytokinesis in T. brucei could potentially be exploited as a new drug target.
  • Posted in Journal of Biological Chemistry, Publications
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