Trypanosoma brucei:Identification of an Internal Region of Phosphoglycerate Kinase Required for Targeting to Glycosomal Microbodies

Peterson, Gregory C.; Sommer, Jürg M.; Klosterman, Scott; Wang, C.C.; Parsons, Marilyn

doi:10.1006/expr.1996.4114

Cited by 25 publications

(12 citation statements)

References 26 publications

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“…We showed that the lactonase has the PTS1 motif, whereas no obvious peroxisome-targeting motif could be recognized in G6PDH. Possibly, the latter enzyme has a unique, polypeptide-internal sequence that is responsible for its routing to the glycosome, analogous to previous observations on T. brucei triosephosphate isomerase (29) and phosphoglycerate kinase isoenzyme A (30). It has been speculated that such a sequence is not a true topogenic signal, but is rather responsible for the protein's association with a different protein with an authentic PTS, enabling entry into the organelle by a piggy-back mechanism (31).…”

Section: Downloaded Fromsupporting

confidence: 79%

Molecular Characterization of the First Two Enzymes of the Pentose-phosphate Pathway of Trypanosoma brucei

Duffieux¹,

Roy²,

Michels³

et al. 2000

Journal of Biological Chemistry

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Section: Downloaded Fromsupporting

confidence: 79%

Molecular Characterization of the First Two Enzymes of the Pentose-phosphate Pathway of Trypanosoma brucei

Duffieux¹,

Roy²,

Michels³

et al. 2000

Journal of Biological Chemistry

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“…The puncta could also represent non‐specific aggregation due to the c‐myc epitope tag. Four reasons argue against this: first, ACC‐myc showed the same fractionation pattern as native ACC, suggesting that the myc tag has no significant effect upon the subcellular distribution of ACC; second, ACC‐myc immunoprecipitates possess ACC activity, suggesting that the myc tag did not affect enzyme function; third, because the myc tag was incorporated into the genomic locus, ACC‐myc is likely expressed at endogenous levels rather than at the high levels associated with epitope‐tag artefacts; fourth, one previous report of a cytosolic myc‐tagged protein showed diffuse staining in T. brucei rather than the puncta we observe for ACC (Peterson et al ., 1997).…”

Section: Discussionmentioning

confidence: 97%

Requirement for acetyl‐CoA carboxylase in Trypanosoma brucei is dependent upon the growth environment

Vigueira

Paul²

2011

Molecular Microbiology

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Summary Trypanosoma brucei, the causative agent of human African trypanosomiasis, possesses two fatty acid synthesis pathways: a major de novo synthesis pathway in the ER and a mitochondrial pathway. The 2-carbon donor for both pathways is malonyl-CoA, which is synthesized from acetyl-CoA by Acetyl-CoA Carboxylase (ACC). Here, we show that T. brucei ACC shares the same enzyme architecture and moderate ~30% identity with yeast and human ACCs. ACC is cytoplasmic and appears to be distributed throughout the cell in numerous puncta distinct from glycosomes and other organelles. ACC is active in both bloodstream and procyclic forms. Reduction of ACC activity by RNA interference (RNAi) resulted in a stage-specific phenotype. In procyclic forms, ACC RNAi resulted in 50-75% reduction in fatty acid elongation and a 64% reduction in growth in low lipid media. In bloodstream forms, ACC RNAi resulted in a minor 15% decrease in fatty acid elongation and no growth defect in culture, even in low lipid media. However, ACC RNAi did attenuate virulence in a mouse model of infection. Thus the requirement for ACC in T. brucei is dependent upon the growth environment in two different life cycle stages.

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“…A minor glycosomal PGK isoenzyme (PGK-A) is targeted to the glycosomes by an internal sequence located between amino acids 24 and 91 [272]. A minor glycosomal PGK isoenzyme (PGK-A) is targeted to the glycosomes by an internal sequence located between amino acids 24 and 91 [272].…”

Section: Pts1mentioning

confidence: 99%

Biogenesis of peroxisomes and glycosomes: trypanosomatid glycosome assembly is a promising new drug target

et al. 2004

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In trypanosomatids (Trypanosoma and Leishmania), protozoa responsible for serious diseases of mankind in tropical and subtropical countries, core carbohydrate metabolism including glycolysis is compartmentalized in peculiar peroxisomes called glycosomes. Proper biogenesis of these organelles and the correct sequestering of glycolytic enzymes are essential to these parasites. Biogenesis of glycosomes in trypanosomatids and that of peroxisomes in other eukaryotes, including the human host, occur via homologous processes involving proteins called peroxins, which exert their function through multiple, transient interactions with each other. Decreased expression of peroxins leads to death of trypanosomes. Peroxins show only a low level of sequence conservation. Therefore, it seems feasible to design compounds that will prevent interactions of proteins involved in biogenesis of trypanosomatid glycosomes without interfering with peroxisome formation in the human host cells. Such compounds would be suitable as lead drugs against trypanosomatid-borne diseases.

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Trypanosoma brucei:Identification of an Internal Region of Phosphoglycerate Kinase Required for Targeting to Glycosomal Microbodies

Cited by 25 publications

References 26 publications

Molecular Characterization of the First Two Enzymes of the Pentose-phosphate Pathway of Trypanosoma brucei

Molecular Characterization of the First Two Enzymes of the Pentose-phosphate Pathway of Trypanosoma brucei

Requirement for acetyl‐CoA carboxylase in Trypanosoma brucei is dependent upon the growth environment

Biogenesis of peroxisomes and glycosomes: trypanosomatid glycosome assembly is a promising new drug target

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