Why and how trypanosomes build a Flagellar Pocket Collar

Sleeping sickness (also known as Human African trypanosomiasis) is caused by the protist parasite Trypanosoma brucei and threatens millions of people in all sub-Saharan African countries. Once the parasite enters the central nervous system and brain, it leads to behavioral changes, poor coordination, confusion, and sleep disturbances (i.e. sleeping sickness). Without diagnosis and treatment, T. brucei infection will almost certainly cause the death of an infected human. T. brucei belongs to the unicellular kinetoplastids and possesses a single flagellum for its motility, viability, transmission and pathogenesis. At the base of the flagellum is a unique belt- like cytoskeletal structure called the flagellar pocket collar (FPC), which is essential for the biogenesis of the flagellar pocket (FP). The FP is an invagination of the plasma membrane and the sole site for all endo- and exocytic activity of the parasite; as such it is indispensable for the survival of the parasite. The BILBO1 protein was the first identified component of the FPC by Dr. Bonhivers and colleagues at the University of Bordeaux in 2008. Dr. Dong and colleagues at the Max Perutz Labs in Vienna have later extensively characterized the structure of T. brucei BILBO1 and revealed that it forms a dumbbell-like tetramer that further assembles into an enormously long and spiral-like filament. The oligomeric structure of BILBO1 acts as a scaffold to recruit many other FPC components, which altogether regulate cytokinesis and viability of the parasite. However, the detailed organization of the BILBO1 filament within the FPC is still unknown, and the majority of the recently identified FPC components and their interaction have not been characterized. With their complimentary expertise, the Dong lab in Vienna and the Bonhivers lab in Bordeaux have established a close collaboration over the past few years. The two groups will continue their productive collaboration in the future to carry out extensive and in-depth investigations on the assembly and function of the FPC in T. brucei. The data obtained from their structural and functional studies will explain how a new FPC is formed, why it is essential, which polymers/proteins are needed, and how they interact. These studies will illuminate the remodeling of the FPC in the context of flagellum and FP biogenesis, and may provide guidance for future therapeutic interventions to effectively control sleeping sickness.