关键词: D. melanogaster biochemistry chemical biology glycosylation neuron-glia interactions neuroscience oxidative stress sialylation sialyltransferase voltage-gated sodium channel

Mesh : Animals Drosophila / metabolism Synaptic Transmission / physiology Nervous System Physiological Phenomena Neurons / metabolism Neuroglia / metabolism Polysaccharides / metabolism

来  源:   DOI:10.7554/eLife.78280   PDF(Pubmed)

Abstract:
Modification by sialylated glycans can affect protein functions, underlying mechanisms that control animal development and physiology. Sialylation relies on a dedicated pathway involving evolutionarily conserved enzymes, including CMP-sialic acid synthetase (CSAS) and sialyltransferase (SiaT) that mediate the activation of sialic acid and its transfer onto glycan termini, respectively. In Drosophila, CSAS and DSiaT genes function in the nervous system, affecting neural transmission and excitability. We found that these genes function in different cells: the function of CSAS is restricted to glia, while DSiaT functions in neurons. This partition of the sialylation pathway allows for regulation of neural functions via a glia-mediated control of neural sialylation. The sialylation genes were shown to be required for tolerance to heat and oxidative stress and for maintenance of the normal level of voltage-gated sodium channels. Our results uncovered a unique bipartite sialylation pathway that mediates glia-neuron coupling and regulates neural excitability and stress tolerance.
摘要:
唾液酸化聚糖的修饰可以影响蛋白质功能,控制动物发育和生理的潜在机制。唾液酸化依赖于涉及进化上保守的酶的专用途径,包括CMP-唾液酸合成酶(CSAS)和唾液酸转移酶(SiaT),它们介导唾液酸的活化及其转移到聚糖末端,分别。在果蝇中,CSAS和DSiaT基因在神经系统中发挥作用,影响神经传递和兴奋性。我们发现这些基因在不同的细胞中起作用:CSAS的功能仅限于神经胶质细胞,而DSiaT在神经元中起作用。唾液酸化途径的这种划分允许通过神经胶质介导的神经唾液酸化控制来调节神经功能。唾液酸化基因被证明是对热和氧化应激的耐受性以及维持电压门控钠通道正常水平所必需的。我们的结果揭示了一个独特的双向唾液酸化途径,该途径介导神经胶质-神经元偶联并调节神经兴奋性和应激耐受性。
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