The Drosophila gene brainiac encodes a glycosyltransferase putatively involved in glycosphingolipid synthesis.
The Drosophila genes fringe and brainiac exhibit sequence similarities to glycosyltransferases. Drosophila and mammalian fringe homologs encode UDP-N-acetylglucosamine:fucose-O-Ser beta1,3-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 beta3-glycosyltransferase family with diverse functions. Eleven distinct mammalian homologs have been demonstrated to encode functional enzymes forming beta1-3 glycosidic linkages with different UDP donor sugars and acceptor sugars. The putative mammalian homologs with highest sequence similarity to brainiac encode UDP-N-acetylglucosamine:beta1,3-N-acetylglucosaminyltransferases (beta3GlcNAc-transferases), and in the present study we show that brainiac also encodes a beta3GlcNAc-transferase that uses beta-linked mannose as well as beta-linked galactose as acceptor sugars. The inner disaccharide core structures of glycosphingolipids in mammals (Galbeta1-4Glcbeta1-Cer) and insects (Manbeta1-4Glcbeta1-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 GlcNAcbeta1-3Manbeta1-4Glcbeta1-Cer core structure. Infection of High Five(TM) cells with baculovirus containing full coding brainiac cDNA markedly increased the ratio of GlcNAcbeta1-3Manbeta1-4Glcbeta1-Cer glycolipids compared with Galbeta1-4Manbeta1-4Glcbeta1-Cer found in wild type cells. We suggest that brainiac exerts its biological functions by regulating biosynthesis of glycosphingolipids.
School of Dentistry, University of Copenhagen, Nørre Allé 20, 2200 Copenhagen N, Denmark.
Tilo
T
Schwientek
Birgit
B
Keck
Steven B
SB
Levery
Mads A
MA
Jensen
Johannes W
JW
Pedersen
Hans H
HH
Wandall
Mark
M
Stroud
Stephen M
SM
Cohen
Margarida
M
Amado
Henrik
H
Clausen
D000818:Animals; D016367:Baculoviridae / Q000378:metabolism; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D018076:DNA, Complementary / Q000378:metabolism; D019992:Databases as Topic; D004187:Disaccharides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004330:Drosophila / Q000201:enzymology*; D029721:Drosophila Proteins; D017344:Genes, Insect; D006026:Glycoside Hydrolases / Q000378:metabolism; D006028:Glycosphingolipids / Q000096:biosynthesis*; D016695:Glycosyltransferases / Q000378:metabolism*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D010802:Phylogeny; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013379:Substrate Specificity; D014530:Uridine Diphosphate / Q000378:metabolism
D018076:DNA, Complementary; D004187:Disaccharides; D029721:Drosophila Proteins; D006028:Glycosphingolipids; D008565:Membrane Proteins; C103963:brn protein, Drosophila; D014530:Uridine Diphosphate; D016695:Glycosyltransferases; D006026:Glycoside Hydrolases