Drosophila alpha-1,4-glycosyltransferase (alpha-4GT1) inhibits reaper-mediated apoptosis in the eye.
In a genetic screen, alpha-4GT1 has been identified as a potential enhancer of Hairless-mediated cell death in the eye of Drosophila. alpha-4GT1 encodes an alpha-1,4-glycosyltransferase, known to catalyze the fifth step in a series of ceramide glycosylation events. As reported for other enzymes involved in the glycosylation of ceramide, alpha-4GT1 is strongly expressed during oogenesis and is deposited maternally in the egg. Moreover, the protein is enriched at cell membranes. Unexpectedly, overexpression of alpha-4GT1 does not enhance Hairless-mediated cell death; instead, Hairless enhancement is caused by an allele of Scutoid present on the alpha-4GT1 chromosome. Interestingly, the downregulation of alpha-4GT1 during eye development amplifies cell death induction by the pro-apoptotic gene reaper. Accordingly, overexpression of alpha-4GT1 represses reaper-induced cell death. Thus, alpha-4GT1 appears to be an inhibitor of apoptosis, as has previously been observed for other ceramide glycosylating enzymes, suggesting that it likewise contributes to ceramide anchoring in the membrane.
Protzer
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Universität Hohenheim, Institut für Genetik (240), Garbenstrasse 30, 70599, Stuttgart, Germany.
Preiss
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Nagel
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D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D003433:Crosses, Genetic; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004330:Drosophila / Q000196:embryology / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004625:Embryo, Nonmammalian; D004843:Epistasis, Genetic / Q000502:physiology; D005123:Eye / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D015870:Gene Expression; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009799:Ocular Physiological Phenomena / Q000187:drug effects / Q000235:genetics*; D034741:RNA, Small Interfering / Q000494:pharmacology
D029721:Drosophila Proteins; D034741:RNA, Small Interfering; C086973:rpr protein, Drosophila; D016695:Glycosyltransferases; C544529:alpha4GT1 protein, Drosophila