Authors
Y L Zhang1; C Y He1; 1 National University of Singapore, Singapore Discussion
The small GTPase Arl13b is associated with Joubert’s Syndrome – a severe genetic disease caused by defective cilia. Previous studies using animal models have shown that Arl13b localizes to the cilium and is important for various cilia-related processes. Molecular mechanisms behind its plethora of phenotypes however is only at the very early stage. We have utilized the versatile T. brucei model to study the Arl13b functions in an early diverged, single-flagellated organism. Our results show that TbArl13b is a flagellar protein crucial for cell motility, flagellum attachment/FAZ assembly, flagellum biogenesis and cell survival. Distinctively among other eukaryotic organisms, TbArl13b associates with the axoneme rather than the flagellar membrane. A Dimerization/Docking domain is necessary and sufficient for this association and localization. Cytoplasmic TbArl13b lacking the D/D domain fail to restore cell growth under TbArl13b RNAi. However, substituting the D/D domain with a flagellar membrane targeting domain creates a viable alternative to WT TbArl13b, suggesting that enrichment in the flagellar compartment rather than the specific sub-flagellum localization is critical for TbArl13b functions. 
