Related Experiment Video
Updated: Jun 28, 2025
06:13
Determination of Glucan Chain Length Distribution of Glycogen Using the Fluorophore-Assisted Carbohydrate Electrophoresis FACE Method
Published on: March 31, 2022
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Deficient glycan extension and endoplasmic reticulum stresses in ALG3-CDG
Earnest J P Daniel1, Andrew C Edmondson2, Yair Argon1
1Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Journal of Inherited Metabolic Disease
|April 10, 2024
Summary
Congenital disorder of glycosylation ALG3-CDG impairs endoplasmic reticulum stress response. This study reveals increased UPR and altered glycans, impacting disease pathogenesis.
Area of Science:
- Biochemistry
- Molecular Biology
- Human Genetics
Background:
- ALG3-CDG is a rare congenital disorder of glycosylation (CDG) affecting neurological function, liver enzymes, and immunity.
- The ALG3 enzyme is crucial for endoplasmic reticulum (ER) glycan extension, a key response to ER stress.
Purpose of the Study:
- To investigate the biochemical consequences of ALG3 deficiency in ALG3-CDG.
- To explore the impact of impaired glycan extension on the unfolded protein response (UPR) and glycoprotein structures.
Main Methods:
- Analysis of patient-derived cultured skin fibroblasts.
- Assessment of UPR activation via the IRE1-α pathway.
- Glycomic analysis of cellular and plasma glycoproteins.
Main Results:
- Elevated UPR and ER-associated degradation activities were observed in ALG3-CDG fibroblasts.
- Constitutive activation of the IRE1-α pathway in UPR.
- Increased N-linked Man3-4 glycans in glycoproteins and identification of a novel processed glycan structure on transferrin.
Conclusions:
- Impaired glycan extension in ALG3-CDG leads to UPR activation and altered glycoprotein profiles.
- These findings provide new insights into the pathogenesis of ALG3-CDG.
- The study highlights the critical role of ALG3 in maintaining ER homeostasis and normal glycosylation.
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