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

被引:79
作者
Hendriks, EF
Robinson, DR
Hinkins, M
Matthews, KR
机构
[1] Univ Manchester, Sch Biol Sci, Manchester M13 9PT, Lancs, England
[2] Univ Bordeaux 2, Mol Parasitol Lab, CNRS, UMR 5016, F-33076 Bordeaux, France
关键词
CCCH protein; differentiation; morphology; Trypanosoma brucei;
D O I
10.1093/emboj/20.23.6700
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cell differentiation in Ttypanosoma 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.
引用
收藏
页码:6700 / 6711
页数:12
相关论文
共 34 条
[1]   A novel epitope tag system to study protein targeting and organelle biogenesis in Trypanosoma brucei [J].
Bastin, P ;
Bagherzadeh, A ;
Matthews, KR ;
Gull, K .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1996, 77 (02) :235-239
[2]   Vectors for inducible expression of toxic gene products in bloodstream and procyclic Trypanosoma brucei [J].
Biebinger, S ;
Wirtz, LE ;
Lorenz, P ;
Clayton, C .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1997, 85 (01) :99-112
[3]  
BROWN R C, 1973, International Journal for Parasitology, V3, P691, DOI 10.1016/0020-7519(73)90095-7
[4]  
BRUN R, 1979, ACTA TROP, V36, P289
[5]   Feedback inhibition of macrophage tumor necrosis factor-α production by tristetraprolin [J].
Carballo, E ;
Lai, WS ;
Blackshear, PJ .
SCIENCE, 1998, 281 (5379) :1001-1005
[6]   CELL-DIFFERENTIATION IN NAEGLERIA-GRUBERI [J].
FULTON, C .
ANNUAL REVIEW OF MICROBIOLOGY, 1977, 31 :597-629
[7]   CONTINUOUS CULTIVATION OF TRYPANOSOMA-BRUCEI BLOOD STREAM FORMS IN A MEDIUM CONTAINING A LOW CONCENTRATION OF SERUM-PROTEIN WITHOUT FEEDER CELL-LAYERS [J].
HIRUMI, H ;
HIRUMI, K .
JOURNAL OF PARASITOLOGY, 1989, 75 (06) :985-989
[8]   RAT MONOCLONAL ANTITUBULIN ANTIBODIES DERIVED BY USING A NEW NON-SECRETING RAT-CELL LINE [J].
KILMARTIN, JV ;
WRIGHT, B ;
MILSTEIN, C .
JOURNAL OF CELL BIOLOGY, 1982, 93 (03) :576-582
[9]   Double-stranded RNA interference in Trypanosoma brucei using head-to-head promoters [J].
LaCount, DJ ;
Bruse, S ;
Hill, KL ;
Donelson, JE .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 2000, 111 (01) :67-76
[10]   Interactions of CCCH zinc finger proteins with mRNA - Binding of tristetraprolin-related zinc finger proteins to Au-rich elements and destabilization of mRNA [J].
Lai, WS ;
Carballo, E ;
Thorn, JM ;
Kennington, EA ;
Blackshear, PJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (23) :17827-17837