Gne-depletion in C2C12 myoblasts leads to alterations in glycosylation and myopathogene expression
File(s)
Published version
Author(s)
Neu, Carolin T
Antonopoulos, Aristotelis
Dell, Anne
Haslam, Stuart M
Horstkorte, Rüdiger
Type
Journal Article
Abstract
GNE myopathy is a rare genetic neuromuscular disorder caused by mutations in the GNE gene. The respective gene product, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), is a bifunctional enzyme that initiates endogenous sialic acid biosynthesis. Sialic acids are important building blocks for the glycosylation machinery of cells and are typically found at the terminal ends of glycoprotein N- and O-glycans. The exact pathomechanism of GNE myopathy remains elusive, and a better understanding of the disease is urgently needed for the development of therapeutic strategies. The purpose of this study was to examine the effects of hyposialylation on glycan structures and subsequent downstream effects in the C2C12 Gne knockout cell model. No overall remodeling of N-glycans was observed in the absence of Gne, but differences in glycosaminoglycan expression and O-GlcNAcylation were detected. Expression analysis of myopathogenes revealed concomitant down-regulation of muscle-specific genes. Among the top candidates were the sodium channel protein type 4 subunit α (Scn4a), voltage-dependent L-type calcium channel subunit α-1s (Cacna1s), ryanodine receptor 1 (Ryr1), and glycogen phosphorylase (Pygm), which are associated with excitation-contraction coupling and energy metabolism. The results suggest that remodeling of the glycome could have detrimental effects on intracellular signaling, excitability of skeletal muscle tissue, and glucose metabolism.
Date Issued
2026-01-01
Date Acceptance
2026-01-19
Citation
Cells, 2026, 15 (2)
ISSN
2073-4409
Publisher
MDPI AG
Start Page
199
End Page
199
Journal / Book Title
Cells
Volume
15
Issue
2
Copyright Statement
© 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41597273
PII: cells15020199
Subjects
GNE
GNE-myopathy
N-glycans
glycosylation
myopathogenes
sialic acids
Glycosylation
Animals
Mice
Myoblasts
Cell Line
Polysaccharides
Multienzyme Complexes
Publication Status
Published
Coverage Spatial
Switzerland
Article Number
199
Date Publish Online
2026-01-20