title: The bi-lobe-associated LRRP1 regulates Ran activity in Trypanosoma brucei.
abstract: Cilia and flagella are conserved eukaryotic organelles important for motility and sensory. The RanGTPase, best known for nucleocytoplasmic transport functions, may also play a role in protein trafficking into the specialized flagellar/ciliary compartments, although the regulatory mechanisms controlling Ran activity at the flagellum remain unclear. The unicellular parasite Trypanosoma brucei contains a single flagellum necessary for cell movement, division and morphogenesis. Correct flagellum functions require flagellar attachment to the cell body, which is mediated by a specialized flagellum attachment zone (FAZ) complex that is assembled together with the flagellum during the cell cycle. We have previously identified the leucine-rich-repeat protein 1 LRRP1 on a bi-lobe structure at the proximal base of flagellum and FAZ. LRRP1 is essential for bi-lobe and FAZ biogenesis, consequently affecting flagellum-driven cell motility and division. Here, we show that LRRP1 forms a complex with Ran and a Ran-binding protein, and regulates Ran-GTP hydrolysis in T. brucei. In addition to mitotic inhibition, depletion of Ran inhibits FAZ assembly in T. brucei, supporting the presence of a conserved mechanism that involves Ran in the regulation of flagellum functions in an early divergent eukaryote.
authors.affiliation: Department of Biological Sciences, Centre for BioImaging Sciences, National University of Singapore, 14 Science Drive 4, S1A #06-04, Singapore 117543, Singapore.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Brasseur
authors.affiliation: Department of Biological Sciences, Centre for BioImaging Sciences, National University of Singapore, 14 Science Drive 4, S1A #06-04, Singapore 117543, Singapore.
authors.forename: Shima
authors.initials: S
authors.lastname: Bayat
authors.affiliation: Department of Biological Sciences, Centre for BioImaging Sciences, National University of Singapore, 14 Science Drive 4, S1A #06-04, Singapore 117543, Singapore.
authors.forename: Xiu Ling
authors.initials: XL
authors.lastname: Chua
authors.affiliation: Department of Biological Sciences, Centre for BioImaging Sciences, National University of Singapore, 14 Science Drive 4, S1A #06-04, Singapore 117543, Singapore.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: University of Texas Medical School.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Singapore Mechanobiology Institute, National University of Singapore, T-Lab, #10-01, 5A Engineering Drive 1, Singapore 117411, Singapore.
authors.forename: Boon Chuan
authors.initials: BC
authors.lastname: Low
authors.affiliation: Department of Biological Sciences, Centre for BioImaging Sciences, National University of Singapore, 14 Science Drive 4, S1A #06-04, Singapore 117543, Singapore dbshyc@nus.edu.sg.
authors.forename: Cynthia Y
authors.initials: CY
authors.lastname: He
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005407:Flagella / Q000378:metabolism*; D008969:Molecular Sequence Data; D012097:Repressor Proteins / Q000378:metabolism*; D014346:Trypanosoma brucei brucei / Q000378:metabolism*; D020931:ran GTP-Binding Protein / Q000378:metabolism*
chemical_list: D012097:Repressor Proteins; D020931:ran GTP-Binding Protein
keywords: Bi-lobe; Flagellum; LRRP1; Ran; RanBP