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.
Schwientek
Tilo
T
School of Dentistry, University of Copenhagen, Nørre Allé 20, 2200 Copenhagen N, Denmark.
Keck
Birgit
B
Levery
Steven B
SB
Jensen
Mads A
MA
Pedersen
Johannes W
JW
Wandall
Hans H
HH
Stroud
Mark
M
Cohen
Stephen M
SM
Amado
Margarida
M
Clausen
Henrik
H
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