Requirement for a core 1 galactosyltransferase in the Drosophila nervous system

Abstract

Mucin type O-glycosylation is a widespread modification of eukaryotic proteins, but its functional requirements remain incompletely understood. It is initiated by the attachment of N-acetylgalactosamine (GalNAc) to Ser or Thr residues, and then elongated by additional sugars. We have examined requirements for mucin-type glycosylation in Drosophila by characterizing the expression and phenotypes of core 1 galactosyltransferases (core 1 GalTs), which elongate O-GalNAc by adding galactose in a ␤1,3 linkage. Drosophila encode several putative core 1 GalTs, each expressed in distinct patterns. CG9520 (C1GalTA) is expressed in the amnioserosa and central nervous system. A null mutation in C1GalTA is lethal, and mutant animals exhibit a striking morphogenetic defect in which the ventral nerve cord is greatly elongated and the brain hemispheres are misshapen. Lectin staining and blotting experiments confirmed that C1GalTA contributes to the synthesis of Gal-␤1,3-GalNAc in vivo. Our results identify a role for mucin-type Oglycosylation during neural development in Drosophila. Developmental Dynamics 237:3703-3714, 2008.

Identification of Genes Required for Neural-Specific Glycosylation Using Functional Genomics

“…The VNC longitudinal length-to-width ratio was significantly shorter in fucTA mutants compared to wild-type larvae. To our knowledge, this is the first report of such shortened VNC in the loss-of-function mutant, although elongated VNC has already been reported in mutants for integrin [ 30 ], collagen IV [ 31 ], DHR3 [ 32 ], worniu [ 33 ] and C1GalTA [ 34 ]. Interestingly, C1GalTA encodes a core 1 galactosyltransferase that adds galactose to O -GalNAc attached to Ser or Thr protein residues.…”

Meigo governs dendrite targeting specificity by modulating Ephrin level and N-glycosylation

“…We found that mutant MARCM clones of glycosyltransferases necessary for the mucin-type O -glycan 32 , sialylated carbohydrates 33 , heparan sulfate proteoglycans and chondroitin sulfate proteoglycans 34–36 did not exhibit dendrite mistargeting along the mediolateral axis like meigo 1 ( Supplementary Table 1 ). On the other hand, the mutant MARCM clones for fused lobes 37 encoding an N -acetylglucosaminidase, which is required for the maturation of N -glycans, showed a cell lethal phenotype.…”

Short stop mediates axonal compartmentalization of mucin-type core 1 glycans

“…Laminin B2, which is a major component of the extracellular matrix, has been reported as a protein that carries T antigens in Drosophila neurons 15 26 . However, it is a secreted protein.…”

“…Recently, we reported that T antigen is involved in the localization of neuromuscular junction (NMJ) boutons and in the synaptogenesis of NMJs 14 . Another group reported that loss of Drosophila C1 β 3GalT1 causes elongation of the ventral nerve cord and malformation of hemispheres in the brain 15 . The results indicate that T antigen plays a significant role in the formation of neural networks.…”