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PMID:20445073

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Citation

Repnikova, E, Koles, K, Nakamura, M, Pitts, J, Li, H, Ambavane, A, Zoran, MJ and Panin, VM (2010) Sialyltransferase regulates nervous system function in Drosophila. J. Neurosci. 30:6466-76

Abstract

In vertebrates, sialylated glycans participate in a wide range of biological processes and affect the development and function of the nervous system. While the complexity of glycosylation and the functional redundancy among sialyltransferases provide obstacles for revealing biological roles of sialylation in mammals, Drosophila possesses a sole vertebrate-type sialyltransferase, Drosophila sialyltransferase (DSiaT), with significant homology to its mammalian counterparts, suggesting that Drosophila could be a suitable model to investigate the function of sialylation. To explore this possibility and investigate the role of sialylation in Drosophila, we inactivated DSiaT in vivo by gene targeting and analyzed phenotypes of DSiaT mutants using a combination of behavioral, immunolabeling, electrophysiological, and pharmacological approaches. Our experiments demonstrated that DSiaT expression is restricted to a subset of CNS neurons throughout development. We found that DSiaT mutations result in significantly decreased life span, locomotor abnormalities, temperature-sensitive paralysis, and defects of neuromuscular junctions. Our results indicate that DSiaT regulates neuronal excitability and affects the function of a voltage-gated sodium channel. Finally, we showed that sialyltransferase activity is required for DSiaT function in vivo, which suggests that DSiaT mutant phenotypes result from a defect in sialylation of N-glycans. This work provided the first evidence that sialylation has an important biological function in protostomes, while also revealing a novel, nervous system-specific function of alpha2,6-sialylation. Thus, our data shed light on one of the most ancient functions of sialic acids in metazoan organisms and suggest a possibility that this function is evolutionarily conserved between flies and mammals.

Links

PubMed PMC3354699 Online version:10.1523/JNEUROSCI.5253-09.2010

Keywords

Animals; Behavior, Animal/physiology; Central Nervous System/anatomy & histology; Central Nervous System/growth & development; Central Nervous System/metabolism; Central Nervous System/physiology; Drosophila/enzymology; Drosophila/physiology; Gait Disorders, Neurologic/genetics; Gene Expression Regulation, Developmental; Genes, Insect/physiology; Longevity/genetics; Mutation; Neuromuscular Junction/genetics; Neuromuscular Junction/physiology; Neurons/metabolism; Neurons/physiology; Sialyltransferases/genetics; Sialyltransferases/physiology; Sodium Channels/genetics; Sodium Channels/physiology; Synaptic Potentials/genetics; Synaptic Potentials/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:Q3YNC8

involved_in

GO:0007528: neuromuscular junction development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9W121

involved_in

GO:0007528: neuromuscular junction development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q9GU23

involved_in

GO:0007528: neuromuscular junction development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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