A novel CCCH protein which modulates differentiation of Trypanosoma bruceito its procyclic form

Cell differentiation in Ttypanosoma brucei involves highly regulated change s in morphology, proliferation and metabolism. However, the controls of the se developmental processes are unknown. We have identified two novel protei ns from the rare CCCH zinc finger family, each <140 amino acids in length a nd implicated in life cycle regulation. TbZFP1 is transiently enriched duri ng differentiation from the bloodstream to procyclic form, whereas tbZFP2, when ablated in bloodstream forms by RNA interference, inhibits this develo pmental step. Moreover, expressing an ectopic copy of tbZFP2 results in a d ramatic procyclic stage-specific remodelling of the trypanosome cytoskeleto n similar to the morphogenic events of differentiation. This phenotype, we term 'nozzle', involves polar extension of microtubules at the posterior en d of the cell and is dependent upon a motif hitherto restricted to E3 ubiqu itin ligases. TbZFP1 and tbZFP2 represent the first molecules implicated in the control of trypanosome differentiation to the procyclic form.