Journal article
A Function for a Specific Zinc Metalloprotease of African Trypanosomes
PLoS pathogens, Vol.3(10), pp.1432-1445
10/2007
DOI: 10.1371/journal.ppat.0030150
PMCID: PMC2034397
PMID: 17953481
Abstract
The
Trypanosoma brucei
genome encodes three groups of zinc metalloproteases, each of which contains ∼30% amino acid identity with the major surface protease (MSP, also called GP63) of
Leishmania
. One of these proteases, TbMSP-B, is encoded by four nearly identical, tandem genes transcribed in both bloodstream and procyclic trypanosomes. Earlier work showed that RNA interference against
TbMSP-B
prevents release of a recombinant variant surface glycoprotein (VSG) from procyclic trypanosomes. Here, we used gene deletions to show that TbMSP-B and a phospholipase C (GPI-PLC) act in concert to remove native VSG during differentiation of bloodstream trypanosomes to procyclic form. When the four tandem
TbMSP-B
genes were deleted from both chromosomal alleles, bloodstream
B
−/−
trypanosomes could still differentiate to procyclic form, but VSG was removed more slowly and in a non-truncated form compared to differentiation of wild-type organisms. Similarly, when both alleles of the single-copy GPI-PLC gene were deleted, bloodstream
PLC
−/−
cells could still differentiate. However, when all the genes for both TbMSP-B and GPI-PLC were deleted from the diploid genome, the bloodstream
B
−/−
PLC
−/−
trypanosomes did not proliferate in the differentiation medium, and 60% of the VSG remained on the cell surface. Inhibitors of cysteine proteases did not affect this result. These findings demonstrate that removal of 60% of the VSG during differentiation from bloodstream to procyclic form is due to the synergistic activities of GPI-PLC and TbMSP-B.
Details
- Title: Subtitle
- A Function for a Specific Zinc Metalloprotease of African Trypanosomes
- Creators
- Paul M Grandgenett - University of Georgia, United States of AmericaKeiko Otsu - University of Georgia, United States of AmericaHelen R Wilson - University of Georgia, United States of AmericaMary E Wilson - University of Georgia, United States of AmericaJohn E Donelson - University of Georgia, United States of America
- Resource Type
- Journal article
- Publication Details
- PLoS pathogens, Vol.3(10), pp.1432-1445
- DOI
- 10.1371/journal.ppat.0030150
- PMID
- 17953481
- PMCID
- PMC2034397
- NLM abbreviation
- PLoS Pathog
- ISSN
- 1553-7366
- eISSN
- 1553-7374
- Publisher
- Public Library of Science; San Francisco, USA
- Alternative title
- A Trypanosome Metalloprotease
- Language
- English
- Date published
- 10/2007
- Academic Unit
- Microbiology and Immunology; International Programs; Epidemiology; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984001219202771
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