A novel CCCH protein which modulates differentiation of Trypanosoma brucei to its procyclic form.
Cell differentiation in Trypanosoma brucei involves highly regulated changes in morphology, proliferation and metabolism. However, the controls of these developmental processes are unknown. We have identified two novel proteins from the rare CCCH zinc finger family, each <140 amino acids in length and implicated in life cycle regulation. TbZFP1 is transiently enriched during differentiation from the bloodstream to procyclic form, whereas tbZFP2, when ablated in bloodstream forms by RNA interference, inhibits this developmental step. Moreover, expressing an ectopic copy of tbZFP2 results in a dramatic procyclic stage-specific remodelling of the trypanosome cytoskeleton similar to the morphogenic events of differentiation. This phenotype, we term 'nozzle', involves polar extension of microtubules at the posterior end of the cell and is dependent upon a motif hitherto restricted to E3 ubiquitin ligases. TbZFP1 and tbZFP2 represent the first molecules implicated in the control of trypanosome differentiation to the procyclic form.
Hendriks
E F
EF
School of Biological Sciences, 2.205 Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Robinson
D R
DR
Hinkins
M
M
Matthews
K R
KR
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D003599:Cytoskeleton / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics; D008025:Ligases / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics; D012313:RNA / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014346:Trypanosoma brucei brucei / Q000378:metabolism / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases; D016335:Zinc Fingers
D017931:DNA Primers; D004268:DNA-Binding Proteins; D015800:Protozoan Proteins; C444079:zinc finger protein 1, Trypanosoma brucei; C444080:zinc finger protein 2, Trypanosoma brucei; D012313:RNA; D044767:Ubiquitin-Protein Ligases; D008025:Ligases