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Drosophila egghead Encodes a β1,4-Mannosyltransferase Predicted to Form the Immediate Precursor Glycosphingolipid Substrate for brainiac

2003; Elsevier BV; Volume: 278; Issue: 3 Linguagem: Inglês

10.1074/jbc.c200619200

1083-351X

Hans H. Wandall, Johannes W. Pedersen, Chaeho Park, Steven B. Levery, Sandrine Pizette, Stephen M. Cohen, Tilo Schwientek, Henrik Clausen,

Lysosomal Storage Disorders Research

The neurogenic Drosophila genes brainiac and egghead are essential for epithelial development in the embryo and in oogenesis. Analysis of egghead and brainiac mutants has led to the suggestion that the two genes function in a common signaling pathway. Recently, brainiac was shown to encode a UDP- N -acetylglucosamine:βManβ1,3- N -acetylglucosaminyltransferase (β3GlcNAc-transferase) tentatively assigned a key role in biosynthesis of arthroseries glycosphingolipids and forming the trihexosylceramide, GlcNAcβ1–3Manβ1–4Glcβ1–1Cer. In the present study we demonstrate that egghead encodes a Golgi-located GDP-mannose:βGlcβ1,4-mannosyltransferase tentatively assigned a biosynthetic role to form the precursor arthroseries glycosphingolipid substrate for Brainiac, Manβ1–4Glcβ1–1Cer. Egghead is unique among eukaryotic gly- cosyltransferase genes in that homologous genes are limited to invertebrates, which correlates with the exclusive existence of arthroseries glycolipids in invertebrates. We propose that brainiac and egghead function in a common biosynthetic pathway and that inactivating mutations in either lead to sufficiently early termination of glycolipid biosynthesis to inactivate essential functions mediated by glycosphingolipids.