title: An EF-hand-containing Protein in Trypanosoma brucei Regulates Cytokinesis Initiation by Maintaining the Stability of the Cytokinesis Initiation Factor CIF1.
abstract: Trypanosoma brucei undergoes cytokinesis uni-directionally from the anterior tip of the new flagellum attachment zone (FAZ) toward the posterior end of the cell. We recently delineated a novel signaling pathway composed of polo-like kinase, cytokinesis initiation factor 1 (CIF1), and aurora B kinase that acts in concert at the new FAZ tip to regulate cytokinesis initiation. To identify new cytokinesis regulators, we carried out proximity-dependent biotin identification and identified many CIF1 binding partners and near neighbors. Here we report a novel CIF1-binding protein, named CIF2, and its mechanistic role in cytokinesis initiation. CIF2 interacts with CIF1 in vivo and co-localizes with CIF1 at the new FAZ tip during early cell cycle stages. RNAi of CIF2 inhibited the normal, anterior-to-posterior cytokinesis but activated an alternative, posterior-to-anterior cytokinesis. CIF2 depletion destabilized CIF1 and disrupted the localization of polo-like kinase and aurora B kinase to the new FAZ tip, thus revealing the mechanistic role of CIF2 in cytokinesis initiation. Surprisingly, overexpression of CIF2 also inhibited the normal, anterior-to-posterior cytokinesis and triggered the alternative, posterior-to-anterior cytokinesis, suggesting a tight control of CIF2 protein abundance. These results identified a new regulator in the cytokinesis regulatory pathway and reiterated that a backup cytokinesis pathway is activated by inhibiting the normal cytokinesis pathway.
authors.affiliation: From the Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas 77030.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: From the Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas 77030.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Hu
authors.affiliation: From the Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas 77030 Ziyin.Li@uth.tmc.edu.
authors.forename: Ziyin
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D048749:Cytokinesis / Q000502:physiology*; D008855:Microscopy, Electron, Scanning; D015800:Protozoan Proteins / Q000235:genetics / Q000502:physiology*; D014346:Trypanosoma brucei brucei / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins
keywords: Trypanosoma brucei; aurora B kinase; backup cytokinesis; cell biology; cell cycle; cytokinesis; microbiology; polo-like kinase