The unusual flagellar targeting mechanism and functions of the trypanosome orthologue of the ciliary GTPase Arl13b

Abstract

The small GTPase Arl13b is one of the most conserved and ancient ciliary proteins. In human and animals, Arl13b is primarily associated with the ciliary membrane, where it acts as a Guanine-nucleotide Exchange Factor (GEF) for Arl3 and is implicated in a variety of ciliary and cellular functions. We have identified and characterized TbArl13, the sole Arl13b homologue in the evolutionarily divergent, protozoan parasite Trypanosoma brucei. TbArl13 has conserved flagellar functions and exhibits catalytic activity towards two different TbArl3 homologues. However, TbArl13 is distinctly associated with the axoneme through a dimerization/docking (D/D) domain. Replacing the D/D domain with a flagellar membrane protein created a viable alternative to the wild-type TbArl13 in our RNA interference (RNAi)-based rescue assay. Therefore, flagellar enrichment is crucial for TbArl13 but mechanisms to achieve this could be flexible. Our findings thus extended the understanding of Arl13b and Arl13b-Arl3 pathway in a divergent flagellate of medical importance.