Glia-neuron coupling via a bipartite sialylation pathway promotes neural transmission and stress tolerance in Drosophila
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been uploaded to a public repository for Tables 1 and Supplementary Table 3
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Larval brin in WT, CSAS, SiaTGlycoPOST GPST000260.
Article and author information
Author details
Funding
National Institutes of Health (NS099409)
- Vladislav Panin
National Institutes of Health (NS075534)
- Vladislav Panin
TAMU-COANCYT (2012-037(S))
- Vladislav Panin
TAMU AgriLife IHA
- Vladislav Panin
National Institutes of Health (GM103490)
- Michael Tiemeyer
Radboud Consortium for Glycoscience
- Dirk Lefeber
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Vilaiwan M Fernandes, University College London, United Kingdom
Version history
- Received: March 1, 2022
- Preprint posted: March 29, 2022 (view preprint)
- Accepted: March 16, 2023
- Accepted Manuscript published: March 22, 2023 (version 1)
- Version of Record published: April 17, 2023 (version 2)
Copyright
© 2023, Scott et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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