Functional roles for beta1,4-N-acetlygalactosaminyltransferase-A in Drosophila larval neurons and muscles.
Adult Drosophila mutant for the glycosyltransferase beta1,4-N-acetlygalactosaminyltransferase-A (beta4GalNAcTA) 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 beta4GalNAcTA 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 hypercontraction 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 hypercontraction could occur. All of these phenotypes can be rescued by a transgene carrying the beta4GalNAcTA 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 neuromuscular junction bouton number, suggesting that this defect arises from cooperation between nerve and muscle. Altogether, these results suggest that beta4GalNAcTA has at least three distinct functional roles.
Haines
Nicola
N
Department of Biology, University of Toronto, Mississauga, Ontario L5L 1C6, Canada. nhaines@utm.utoronto.ca
Stewart
Bryan A
BA
D000818:Animals; D001522:Behavior, Animal; D002118:Calcium / Q000378:metabolism; D048429:Cell Size; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology*; D019706:Excitatory Postsynaptic Potentials; D007814:Larva / Q000201:enzymology; D009119:Muscle Contraction; D009132:Muscles / Q000201:enzymology*; D009154:Mutation / Q000235:genetics; D017350:N-Acetylgalactosaminyltransferases / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000166:cytology; D009474:Neurons / Q000201:enzymology*; D010641:Phenotype; D017729:Presynaptic Terminals; D000097763:Polypeptide N-acetylgalactosaminyltransferase
D002118:Calcium; D029721:Drosophila Proteins; D017350:N-Acetylgalactosaminyltransferases; D000097763:Polypeptide N-acetylgalactosaminyltransferase