title: The role of Drosophila cytidine monophosphate-sialic acid synthetase in the nervous system.
abstract: While sialylation plays important functions in the nervous system, the complexity of glycosylation pathways and limitations of genetic approaches preclude the efficient analysis of these functions in mammalian organisms. Drosophila has recently emerged as a promising model for studying neural sialylation. Drosophila sialyltransferase, DSiaT, was shown to be involved in the regulation of neural transmission. However, the sialylation pathway was not investigated in Drosophila beyond the DSiaT-mediated step. Here we focused on the function of Drosophila cytidine monophosphate-sialic acid synthetase (CSAS), the enzyme providing a sugar donor for DSiaT. Our results revealed that the expression of CSAS is tightly regulated and restricted to the CNS throughout development and in adult flies. We generated CSAS mutants and analyzed their phenotypes using behavioral and physiological approaches. Our experiments demonstrated that mutant phenotypes of CSAS are similar to those of DSiaT, including decreased longevity, temperature-induced paralysis, locomotor abnormalities, and defects of neural transmission at neuromuscular junctions. Genetic interactions between CSAS, DSiaT, and voltage-gated channel genes paralytic and seizure were consistent with the hypothesis that CSAS and DSiaT function within the same pathway regulating neural excitability. Intriguingly, these interactions also suggested that CSAS and DSiaT have some additional, independent functions. Moreover, unlike its mammalian counterparts that work in the nucleus, Drosophila CSAS was found to be a glycoprotein-bearing N-glycans and predominantly localized in vivo to the Golgi compartment. Our work provides the first systematic analysis of in vivo functions of a eukaryotic CSAS gene and sheds light on evolutionary relationships among metazoan CSAS proteins.
authors.affiliation: Department of Biochemistry and Biophysics and Department of Biology, Texas A&M University, College Station, Texas 77843, USA.
authors.forename: Rafique
authors.initials: R
authors.lastname: Islam
authors.forename: Michiko
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hilary
authors.initials: H
authors.lastname: Scott
authors.forename: Elena
authors.initials: E
authors.lastname: Repnikova
authors.forename: Mindy
authors.initials: M
authors.lastname: Carnahan
authors.forename: Dheeraj
authors.initials: D
authors.lastname: Pandey
authors.forename: Courtney
authors.initials: C
authors.lastname: Caster
authors.forename: Saba
authors.initials: S
authors.lastname: Khan
authors.forename: Tina
authors.initials: T
authors.lastname: Zimmermann
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Zoran
authors.forename: Vladislav M
authors.initials: VM
authors.lastname: Panin
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D003568:Cytidine Monophosphate / Q000378:metabolism*; D004330:Drosophila / Q000201:enzymology* / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D008025:Ligases / Q000235:genetics* / Q000378:metabolism; D008136:Longevity / Q000235:genetics; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D000216:N-Acylneuraminate Cytidylyltransferase / Q000235:genetics* / Q000378:metabolism; D009424:Nervous System Physiological Phenomena / Q000235:genetics*; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism; D010243:Paralysis / Q000235:genetics / Q000378:metabolism; D022142:Secretory Vesicles / Q000502:physiology; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology; D013696:Temperature
chemical_list: D029721:Drosophila Proteins; D012799:Sialyltransferases; D000216:N-Acylneuraminate Cytidylyltransferase; D008025:Ligases; D003568:Cytidine Monophosphate; D019158:N-Acetylneuraminic Acid