Biologjia Online

Members of the mammalian ß1,4-galactosyltransferase family are among the best studied glycosyltransferases, but the requirements for all members of this family within an animal have not previously been determined. Here, we describe analysis of two Drosophila genes, ß4GalNAcTA (CG8536) and ß4GalNAcTB (CG14517), that are homologous to mammalian ß1,4-galactosyltransferases. Like their mammalian homologs, these glycosyltransferases use N-acetylglucosamine as an acceptor substrate. However, they transfer N-acetylgalactosamine rather than galactose. This activity, together with amino acid sequence similarity, places them among a group of recently identified invertebrate ß1,4-N-acetylgalactosaminyltransferases. To investigate the biological functions of these genes, null mutations were generated by imprecise excision of a transposable element (ß4GalNAcTA) or by gene-targeted homologous recombination (ß4GalNAcTB). Flies mutant for ß4GalNAcTA are viable and fertile but display behavioral phenotypes suggestive of essential roles for GalNAc-ß1,4-GlcNAc containing glycoconjugates in neuronal and/or muscular function. ß4GalNAcTB mutants are viable and display no evident morphological or behavioral phenotypes. Flies doubly mutant for both genes display only the behavioral phenotypes associated with mutation of ß4GalNAcTA. Thus Drosophila homologs of the mammalian ß4GalT family are essential for neuromuscular physiology or development but are not otherwise required for viability, fertility, or external morphology.