Bloodstream form Trypanosoma brucei depend upon multiple metacaspases associated with RAB11-positive endosomes

被引:89
作者
Helms, MJ
Ambit, A
Appleton, P
Tetley, L
Coombs, GH
Mottram, JC [1 ]
机构
[1] Univ Glasgow, Anderson Coll, Wellcome Ctr Mol Parasitol, Glasgow G11 6NU, Lanark, Scotland
[2] Univ Glasgow, Div Infect & Immun, Inst Biomed & Life Sci, Glasgow G12 8QQ, Lanark, Scotland
基金
英国医学研究理事会;
关键词
metacaspase; endosomes; recycling; Trypanosoma; programmed cell death; RNAi;
D O I
10.1242/jcs.02809
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Trypanosoma brucei possesses five metacaspase genes. Of these, MCA2 and MCA3 are expressed only in the mammalian bloodstream form of the parasite, whereas MCA5 is expressed also in the insect procyclic form. Triple RNAi analysis showed MCA2, MCA3 and MCA5 to be essential in the bloodstream form, with parasites accumulating pre-cytokinesis. Nevertheless, triple null mutants (Delta mca2/3 Delta mca5) could be isolated after sequential gene deletion. Thereafter, Delta mca2/3 Delta mca5 mutants were found to grow well both in vitro in culture and in vivo in mice. We hypothesise that metacaspases are essential for bloodstream form parasites, but they have overlapping functions and their progressive loss can be compensated for by activation of alternative biochemical pathways. Analysis of Delta mca2/3 Delta mca5 revealed no greater or lesser susceptibility to stresses reported to initiate programmed cell death, such as treatment with prostaglandin D2. The metacaspases were found to colocalise with RAB11, a marker for recycling endosomes. However, variant surface glycoprotein (VSG) recycling processes and the degradation of internalised anti-VSG antibody were found to occur similarly in wild type, Delta mca2/3 Delta mca5 and triple RNAi induced parasites. Thus, the data provide no support for the direct involvement of T. brucei metacaspases in programmed cell death and suggest that the proteins have a function associated with RAB11 vesicles that is independent of known recycling processes of RAB11-positive endosomes.
引用
收藏
页码:1105 / 1117
页数:13
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