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Glycosylphosphatidylinositol-specific phospholipase C regulates transferrin endocytosis in the African trypanosome
- Source :
- Biochemical Journal. 417:685-694
- Publication Year :
- 2009
- Publisher :
- Portland Press Ltd., 2009.
-
Abstract
- GPI-PLC (glycosylphosphatidylinositol-specific phospholipase C) is expressed in bloodstream-form Trypanosoma brucei, a protozoan that causes human African trypanosomiasis. Loss of genes encoding GPI-PLC reduces the virulence of a pleomorphic strain of the parasite, for reasons that are not clear. In the present paper, we report that GPI-PLC stimulates endocytosis of transferrin by 300–500%. Surprisingly, GPI-PLC is not detected at endosomes, suggesting that the enzyme does not interact directly with the endosomal machinery. We therefore hypothesized that a diffusible product of the GPI-PLC enzyme reaction [possibly DAG (diacylglycerol)] mediated the biological effects of the protein. Two sets of data support this assertion. First, a catalytically inactive Q81L mutant of GPI-PLC, expressed in a GPI-PLC-null background, had no effect on endocytosis, indicating that enzyme activity is essential for the protein to stimulate endocytosis. Secondly, the exogenous DAGs OAG (1-oleyl-2-acetyl-sn-glycerol) and DMG (dimyristoylglycerol) independently stimulated endocytosis of transferrin. Furthermore, the DAG mimic PMA, a phorbol ester, also activated endocytosis in T. brucei. DAG-stimulated endocytosis is a novel pathway in the trypanosome. We surmise that (i) GPI-PLC regulates transferrin endocytosis in T. brucei, (ii) GPI-PLC is a signalling enzyme, and (iii) DAG is a second messenger for GPI-PLC. We propose that regulation of endocytosis is a physiological function of GPI-PLC in bloodstream T. brucei.
- Subjects :
- Endosome
Trypanosoma brucei brucei
Protozoan Proteins
Transferrin receptor
Trypanosoma brucei
Glycosylphosphatidylinositol Diacylglycerol-Lyase
Endocytosis
Biochemistry
Diglycerides
Phorbol Esters
Animals
Molecular Biology
Diacylglycerol kinase
chemistry.chemical_classification
biology
Phospholipase C
Transferrin
Cell Biology
biology.organism_classification
carbohydrates (lipids)
Microscopy, Fluorescence
chemistry
Glycosylphosphatidylinositol diacylglycerol-lyase
lipids (amino acids, peptides, and proteins)
Subjects
Details
- ISSN :
- 14708728 and 02646021
- Volume :
- 417
- Database :
- OpenAIRE
- Journal :
- Biochemical Journal
- Accession number :
- edsair.doi.dedup.....18de90f1357b052331d3f6d304d20eec
- Full Text :
- https://doi.org/10.1042/bj20080167