TY - JOUR
T1 - Glycosphingolipids with extended sugar chain have specialized functions in development and behavior of Drosophila
AU - Chen, Ya-Wen
AU - Pedersen, Johannes W
AU - Wandall, Hans H
AU - Levery, Steven B
AU - Pizette, Sandrine
AU - Clausen, Henrik
AU - Cohen, Stephen M
N1 - Keywords: Animals; Behavior, Animal; Carbohydrates; Cell Adhesion; Cell Membrane; Cloning, Molecular; Drosophila; Gene Expression Regulation, Developmental; Glycolipids; Glycosphingolipids; Glycosylation; Humans; Models, Genetic; Phylogeny; Substrate Specificity
PY - 2007
Y1 - 2007
N2 - Glycosphingolipids (GSL) are glycosylated polar lipids in cell membranes essential for development of vertebrates as well as Drosophila. Mutants that impair enzymes involved in biosynthesis of GSL sugar chains provide a means to assess the functions of the sugar chains in vivo. The Drosophila glycosyltransferases Egghead and Brainiac are responsible for the 2nd and 3rd steps of GSL sugar chain elongation. Mutants lacking these enzymes are lethal and the nature of the defects that occur has suggested that GSL might impact on signaling by the Notch and EGFR pathways. Here we report on characterization of enzymes involved in the 4th and 5th steps of GSL sugar chain elongation in vitro and explore the biological consequences of removing the enzymes involved in step 4 in vivo. Two beta4-N-Acetylgalactosyltransferase enzymes can carry out step 4 (beta4GalNAcTA and beta4GalNAcTB), and while they may have overlapping activity, the mutants produce distinct phenotypes. The beta4GalNAcTA mutant displays behavioral defects, which are also observed in viable brainiac mutants, suggesting that proper locomotion and coordination primarily depend on GSL elongation. beta4GalNAcTB mutant animal shows ventralization of ovarian follicle cells, which is caused by defective EGFR signaling between the oocyte and the dorsal follicle cells to specify dorsal fate. GSL sequentially elongated by Egh, Brn and beta4GalNAcTB in the oocyte contribute to this signaling pathway. Despite the similar enzymatic activity, we provide evidence that the two enzymes are not functionally redundant in vivo, but direct distinct developmental functions of GSL.
AB - Glycosphingolipids (GSL) are glycosylated polar lipids in cell membranes essential for development of vertebrates as well as Drosophila. Mutants that impair enzymes involved in biosynthesis of GSL sugar chains provide a means to assess the functions of the sugar chains in vivo. The Drosophila glycosyltransferases Egghead and Brainiac are responsible for the 2nd and 3rd steps of GSL sugar chain elongation. Mutants lacking these enzymes are lethal and the nature of the defects that occur has suggested that GSL might impact on signaling by the Notch and EGFR pathways. Here we report on characterization of enzymes involved in the 4th and 5th steps of GSL sugar chain elongation in vitro and explore the biological consequences of removing the enzymes involved in step 4 in vivo. Two beta4-N-Acetylgalactosyltransferase enzymes can carry out step 4 (beta4GalNAcTA and beta4GalNAcTB), and while they may have overlapping activity, the mutants produce distinct phenotypes. The beta4GalNAcTA mutant displays behavioral defects, which are also observed in viable brainiac mutants, suggesting that proper locomotion and coordination primarily depend on GSL elongation. beta4GalNAcTB mutant animal shows ventralization of ovarian follicle cells, which is caused by defective EGFR signaling between the oocyte and the dorsal follicle cells to specify dorsal fate. GSL sequentially elongated by Egh, Brn and beta4GalNAcTB in the oocyte contribute to this signaling pathway. Despite the similar enzymatic activity, we provide evidence that the two enzymes are not functionally redundant in vivo, but direct distinct developmental functions of GSL.
U2 - 10.1016/j.ydbio.2007.04.013
DO - 10.1016/j.ydbio.2007.04.013
M3 - Journal article
C2 - 17498683
SN - 0012-1606
VL - 306
SP - 736
EP - 749
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -