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.

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