Bloodstream form trypanosoma brucei depend upon multiple metacaspases associated with RAB11-positive endosomes
Helms, Matthew J. and Ambit, Audrey and Appleton, Paul and Tetley, Laurence and Coombs, Graham H. and Mottram, Jeremy C. (2006) Bloodstream form trypanosoma brucei depend upon multiple metacaspases associated with RAB11-positive endosomes. Journal of Cell Science, 119 (6). pp. 1105-1117. ISSN 0021-9533 (https://doi.org/10.1242/jcs.02809)
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Abstract
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 (Δmca2/3Δmca5) could be isolated after sequential gene deletion. Thereafter, Δmca2/3Δmca5 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 Δmca2/3Δmca5 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, Δmca2/3Δmca5 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.
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Item type: Article ID code: 10508 Dates: DateEvent15 March 2006Published24 November 2005AcceptedSubjects: Medicine > Pharmacy and materia medica Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Strathprints Administrator Date deposited: 08 Nov 2011 16:26 Last modified: 17 Sep 2024 12:31 URI: https://strathprints.strath.ac.uk/id/eprint/10508