Functional Roles For Beta 1,4-N-Acetlygalactosaminyltransferase-A In Drosophila Larval Neurons And Muscles

Adult Drosophila mutant for the glycosyl transferase beta 1,4-N-acetlygalactosaminyltransferase-A (beta 4Gal-NAcTA) display an abnormal locomotion phenotype, indicating a role for this enzyme, and the glycan Structures that it generates, in the neuromuscular system. To investigate the functional role of this enzyme in more detail, we turned to the accessible larval neuromuscular system and report here that larvae mutant for beta 4GalVAcTA display distinct nerve and muscle phenotypes. Mutant larvae exhibit abnormal backward crawling, reductions in nerve terminal bouton number, decreased spontaneous transmitter-release frequency, and short, wide muscles. This muscle shape change appears to result from hyper-contraction since the individual sarcomeres are shorter in mutant muscles. Analysis of muscle calcium signals showed altered calcium handling in the mutant, suggesting a mechanism by which hyper-contraction could occur. All of these phenotypes can be rescued by a transgene carrying the beta 4GalNAc7A genomic region. Tissue-specific expression, using the Gal4-UAS system, reveals that neural expression rescues the mutant crawling phenotype, while muscle expression rescues the Muscle defect. Tissue-specific expression did not appear to rescue the decrease in neurormuscular junction bouton number, suggesting that this defect arises from cooperation between nerve and muscle. Altogether, these results suggesting that beta 4GalNAcTA has at least three distinct functional roles.