Glia-Neuron Coupling via a Bipartite Sialylation Pathway Promotes Neural Transmission and Stress Tolerance IGlia-Neuron Coupling via a Bipartite Sialylation Pathway Promotes Neural Transmission and Stress Tolerance in Drosophila

Authors

Hilary Scott
Boris Novikov
Berrak Ugur
Brooke Allen
Ilya Mertsalov
Pedro Monagas-Valentin
Melissa Koff
Sarah Baas Robinson
Kazuhiro Aoki
Raisa Veizaj
Dirk J Lefeber
Michael Tiemeyer
Hugo Bellen
Vladislav Panin

Publication Date

3-22-2023

Journal

eLife

DOI

10.7554/eLife.78280

PMID

36946697

PMCID

PMC10110239

PubMedCentral® Posted Date

3-22-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Drosophila, Synaptic Transmission, Nervous System Physiological Phenomena, Neurons, Neuroglia, Polysaccharides, D. melanogaster

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.