Photoreceptor degeneration caused by defects of a ciliary kinase

摘要

Intraflagellar transport (IFT) is a mechanism used for formationof cilia and flagella in eukaryotes and little isknown about its regulation. We propose that a RAB-likeprotein termed RABL4 (IFT27), which is associated withIFT complexes could be involved in IFT regulation. Indeed,since small GTPases are known for being key regulators ofmany trafficking processes. We used different approachesin order to determine the role of RABL4 during flagellumformation in Trypanosoma brucei. First, GFP::RABL4experiments showed that the protein is localized in the cellbody, at the basal body and within the flagellum, like allIFT proteins studied so far in trypanosomes. Bi-directionalmovement of GFP fusion protein was observed in the flagellum.RABL4 silencing demonstrated an essential role inflagellum assembly and revealed a mixture of phenotypes.Some cells do not assemble a flagellum, whereas othersproduce short flagella filled with material looking like IFTcomplexes. The structure of these short flagella is severelyaffected, with disrupted microtubule doublets, mislocalisationof the central pair and impaired PFR (an extraaxonemalstructure) construction. The latter one can beexcessively large, with numerous layers that affect theshape of the flagellum membrane.We propose that RABL4could participate to the loading of flagellar precursors intoIFT complexes for transport and we are currently analyzingGDP or GTP locked versions of the protein to challengethis hypothesis.