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 plays 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. Proper flagellum functions require flagellar attachment to the cell body, which is mediated by a specialized flagellum attachment zone (FAZ) complex assembled together with the flagellum during the cell cycle. We have previously identified a leucine-rich repeats-containing protein, 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 T. brucei Ran inhibits FAZ assembly, supporting the presence of a conserved mechanism involving Ran in the regulation of flagellum functions in an early divergent eukaryote.