Abstract

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:beta Man beta 1,3-N-acetylglucosaminyltransferase (beta 3GlcNAc-transferase) tentatively assigned a key role in biosynthesis of arthroseries glycosphingolipids and forming the trihexosylceramide, GlcNAc beta 1-3Man beta 1-4Glc beta 1-1Cer. In the present study we demonstrate that egghead encodes a Golgi-located GDP-mannose:beta Glc beta 1,4-mannosyltransferase tentatively assigned a biosynthetic role to form the precursor arthroseries glycosphingolipid substrate for Brainiac, Man beta 1-4Glc beta 1-1Cer. Egghead is unique among eukaryotic glycosyltransferase 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.

Highlights

  • From the ‡School of Dentistry, University of Copenhagen, Nørre Alle 20, 2200 Copenhagen N, Denmark, the §Department of Chemistry, University of New Hampshire, Durham, New Hampshire 03824, and the ¶European Molecular Biology Laboratory, Meyerhofstr 1, 69117 Heidelberg, Germany

  • In the present study we demonstrate that egghead encodes a Golgi-located GDP-mannose:␤Glc ␤1,4-mannosyltransferase tentatively assigned a biosynthetic role to form the precursor arthroseries glycosphingolipid substrate for Brainiac, Man␤1– 4Glc␤1– 1Cer

  • 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

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Summary

Accelerated Publication

Drosophila egghead Encodes a ␤1,4-Mannosyltransferase Predicted to Form the Immediate Precursor Glycosphingolipid Substrate for brainiac*. Analysis of egghead and brainiac mutants has led to the suggestion that the two genes function in a common signaling pathway. Yuan et al (5) originally proposed that brainiac together with the distant homologous gene fringe encoded glycosyltransferases. This hypothesis has subsequently proved correct and both represent glycosyltransferases with functionally conserved mammalian homologs (6 –9). In the present study we tested the hypothesis that egghead encodes a unique invertebrate glycosyltransferase activity in the same biosynthetic pathway as brainiac and present evidence that egghead encodes a ␤1,4-mannosyltransferase predicted to form the MacCer precursor glycolipid substrate for brainiac

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