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.
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Research Article|
January 16 2009
Glycosylphosphatidylinositol-specific phospholipase C regulates transferrin endocytosis in the African trypanosome
Sandesh Subramanya;
Sandesh Subramanya
*Department of Cellular Biology, University of Georgia, 724 Biological Sciences Building, Athens, GA 30602, U.S.A.
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C. Frank Hardin;
C. Frank Hardin
*Department of Cellular Biology, University of Georgia, 724 Biological Sciences Building, Athens, GA 30602, U.S.A.
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Dietmar Steverding;
Dietmar Steverding
†BioMedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, U.K.
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Kojo Mensa-Wilmot
Kojo Mensa-Wilmot
1
*Department of Cellular Biology, University of Georgia, 724 Biological Sciences Building, Athens, GA 30602, U.S.A.
1To whom correspondence should be addressed (email mensawil@uga.edu).
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Publisher: Portland Press Ltd
Received:
January 21 2008
Revision Received:
August 28 2008
Accepted:
September 11 2008
Accepted Manuscript online:
September 11 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 417 (3): 685–694.
Article history
Received:
January 21 2008
Revision Received:
August 28 2008
Accepted:
September 11 2008
Accepted Manuscript online:
September 11 2008
Citation
Sandesh Subramanya, C. Frank Hardin, Dietmar Steverding, Kojo Mensa-Wilmot; Glycosylphosphatidylinositol-specific phospholipase C regulates transferrin endocytosis in the African trypanosome. Biochem J 1 February 2009; 417 (3): 685–694. doi: https://doi.org/10.1042/BJ20080167
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