The role of intraflagellar transport in signaling in the African trypanosome Trypanosoma brucei



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The African trypanosome Trypanosoma brucei is the protozoan parasite responsible for African sleeping sickness. It moves through its host by rotating its single flagellum. Intraflagellar transport (IFT) is a highly conserved bidirectional transport along the length of the flagellum which is required for the assembly of flagella in T. brucei and other organisms. IFT has been demonstrated to play an important role in signaling in some organisms, such as Chlamydomonas reinhardtii. Certain migrations are necessary for T. brucei to cause disease in the mammalian host in the process known as pathogenesis. These migrations presumably rely on directed motility mediated by signaling. Moreover, cilia (functional and structural equivalents of flagella) play a sensory role in many tissues and in mammalian development. IFT could be the mechanism which participates in signaling and requires flagella. We hypothesize that in T. brucei retrograde (tip-to-base) IFT carries signals received in the flagellum to the cell body. To interrupt retrograde IFT, we used RNA interference to suppress the translation of two proteins involved in retrograde IFT, DHC1b and IFT140. Since this is an inducible RNA interference system, we could seek an induction time for which cells were still motile but RNA was depleted. Initial work was done to develop an assay based on a novel aggregating behavior termed social motility behavior. The assay could be used to test the ability of motile DHC1b- and IFT140-depleted mutants to aggregate, and thus indirectly measure their ability to signal. Such studies would provide initial insight into the role of IFT in the signaling that mediates the directional migration essential for pathogenesis.



trypanosome, intraflagellar, transport, flagellum, Trypanosoma, brucei