Drosophila egghead encodes a beta 1,4-mannosyltransferase predicted to form the immediate precursor glycosphingolipid substrate for brainiac.
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.
Wandall
Hans H
HH
School of Dentistry, University of Copenhagen, Nørre Allé 20, 2200 Copenhagen N, Denmark.
Pedersen
Johannes W
JW
Park
Chaeho
C
Levery
Steven B
SB
Pizette
Sandrine
S
Cohen
Stephen M
SM
Schwientek
Tilo
T
Clausen
Henrik
H
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D017931:DNA Primers; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D006028:Glycosphingolipids / Q000378:metabolism*; D019476:Insect Proteins / Q000235:genetics* / Q000378:metabolism; D008364:Mannosyltransferases / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D013379:Substrate Specificity
D017931:DNA Primers; D029721:Drosophila Proteins; D006028:Glycosphingolipids; D019476:Insect Proteins; D008565:Membrane Proteins; C103963:brn protein, Drosophila; C103962:egh protein, Drosophila; D008364:Mannosyltransferases; C035777:chitobiosyldiphosphodolichol beta-mannosyltransferase