{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:06:41Z","timestamp":1761523601054},"reference-count":55,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,2,1]]},"abstract":"<jats:p>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\u2013500%. 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.<\/jats:p>","DOI":"10.1042\/bj20080167","type":"journal-article","created":{"date-parts":[[2008,9,12]],"date-time":"2008-09-12T14:12:38Z","timestamp":1221228758000},"page":"685-694","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Glycosylphosphatidylinositol-specific phospholipase C regulates transferrin endocytosis in the African trypanosome"],"prefix":"10.1042","volume":"417","author":[{"given":"Sandesh","family":"Subramanya","sequence":"first","affiliation":[{"name":"Department of Cellular Biology, University of Georgia, 724 Biological Sciences Building, Athens, GA 30602, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.\u00a0Frank","family":"Hardin","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, University of Georgia, 724 Biological Sciences Building, Athens, GA 30602, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dietmar","family":"Steverding","sequence":"additional","affiliation":[{"name":"BioMedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kojo","family":"Mensa-Wilmot","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, University of Georgia, 724 Biological Sciences Building, Athens, GA 30602, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2009,1,16]]},"reference":[{"key":"2021112215092939100_B1","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/nrm883","article-title":"Signal transduction and endocytosis: close encounters of many kinds","volume":"3","author":"Sorkin","year":"2002","journal-title":"Nat. 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