The Drosophila gene brainiac encodes a glycosyltransferase putatively involved in glycosphingolipid synthesis

Abstract

The Drosophila genes fringe and brainiac exhibit sequence similarities to glycosyltransferases. Drosophila and mammalian fringe homologs encode UDP-N-acetylglucosamine:fucose-O-Ser β1,3-N-acetylglucosaminyltransferases that modulate the function of Notch family receptors. The biological function of brainiac is less well understood. brainiac is a member of a large homologous mammalian β3-glycosyltransferase family with diverse functions. Eleven distinct mammalian homologs have been demonstrated to encode functional enzymes forming β1-3 glycosidic linkages with different UDP donor sugars and acceptor sugars. The putative mammalian homologs with highest sequence similarity to brainiac encode UDP-N-acetylglucosamine: β1,3-N-acetylglucosaminyltransferases (β3G1cNAc-transferases), and in the present study we show that brainiac also encodes a β3G1cNAc-transferase that uses β-linked mannose as well as β-linked galactose as acceptor sugars. The inner disaccharide core structures of glycosphingolipids in mammals (Ga1β1-4G1cβ1-Cer) and insects (Manβ1-4G1cβ1-Cer) are different. Both disaccharide glycolipids served as substrates for brainiac, but glycolipids of insect cells have so far only been found to be based on the G1cNAcβ1-3Manβ1-4G1cβ1-Cer core structure. Infection of High Five™ cells with baculovirus containing full coding brainiac cDNA markedly increased the ratio of G1cNAcβ1-3Manβ1-4G1cβ1-Cer glycolipids compared with Ga1β1-4Manβ1-4G1cβ1-Cer found in wild type cells. We suggest that brainiac exerts its biological functions by regulating biosynthesis of glycosphingolipids.