PUBLICATION
Lowered GnT-I Activity Decreases Complex-Type N-Glycan Amounts and Results in an Aberrant Primary Motor Neuron Structure in the Spinal Cord
- Authors
- Hatchett, C.J., Hall, M.K., Messer, A.R., Schwalbe, R.A.
- ID
- ZDB-PUB-240828-6
- Date
- 2024
- Source
- Journal of developmental biology 12(3): (Journal)
- Registered Authors
- Hall, Kristen, Hatchett, Cody, Schwalbe, Ruth
- Keywords
- N-acetylglucosaminyltransferase-I (GnT-I), N-glycans, development, glycomics, motor neurons, oligomannose, spinal cord
- MeSH Terms
- none
- PubMed
- 39189261 Full text @ J Dev Biol
Citation
Hatchett, C.J., Hall, M.K., Messer, A.R., Schwalbe, R.A. (2024) Lowered GnT-I Activity Decreases Complex-Type N-Glycan Amounts and Results in an Aberrant Primary Motor Neuron Structure in the Spinal Cord. Journal of developmental biology. 12(3):.
Abstract
The attachment of sugar to proteins and lipids is a basic modification needed for organismal survival, and perturbations in glycosylation cause severe developmental and neurological difficulties. Here, we investigated the neurological consequences of N-glycan populations in the spinal cord of Wt AB and mgat1b mutant zebrafish. Mutant fish have reduced N-acetylglucosaminyltransferase-I (GnT-I) activity as mgat1a remains intact. GnT-I converts oligomannose N-glycans to hybrid N-glycans, which is needed for complex N-glycan production. MALDI-TOF MS profiles identified N-glycans in the spinal cord for the first time and revealed reduced amounts of complex N-glycans in mutant fish, supporting a lesion in mgat1b. Further lectin blotting showed that oligomannose N-glycans were more prevalent in the spinal cord, skeletal muscle, heart, swim bladder, skin, and testis in mutant fish relative to WT AB, supporting lowered GnT- I activity in a global manner. Developmental delays were noted in hatching and in the swim bladder. Microscopic images of caudal primary (CaP) motor neurons of the spinal cord transiently expressing EGFP in mutant fish were abnormal with significant reductions in collateral branches. Further motor coordination skills were impaired in mutant fish. We conclude that identifying the neurological consequences of aberrant N-glycan processing will enhance our understanding of the role of complex N-glycans in development and nervous system health.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping