Glia-neuron coupling via a bipartite sialylation pathway promotes neural transmission and stress tolerance in <i>Drosophila</i>.

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 <i>Drosophila</i>, <i>CSAS</i> and <i>DSiaT</i> genes function in the nervous system, affecting neural transmission and excitability. We found that these genes function in different cells: the function of <i>CSAS</i> is restricted to glia, while <i>DSiaT</i> 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.