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Protein glycosylation in development and disease
J W Dennis1, M Granovsky, C E Warren
1Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Summary
Glycans on cell surfaces are crucial for communication in development and disease. This review explores how mutations in glycosylation enzymes impact glycoprotein function and suggests potential therapeutic targets.
Area of Science:
- Biochemistry
- Glycobiology
- Molecular Biology
Background:
- N- and O-linked glycans on glycoproteins mediate cell-cell communication, influencing development and disease.
- Metazoan N-glycan biosynthesis is complex, involving medial-Golgi beta-N-acetylglucosaminyltransferases (GlcNAc-Ts).
- Glycosyltransferase regulation in the Golgi generates glycoprotein diversity, affecting molecular properties and biological activity.
Purpose of the Study:
- To review the molecular functions of glycan structures.
- To understand how mutations in glycosylation impact glycoprotein activity.
- To explore the therapeutic potential of targeting GlcNAc-Ts.
Main Methods:
- Examination of targeted mutations affecting glycosylation in mice.
- Analysis of congenital mutations in humans.
- Review of existing literature on glycan structure-function relationships.
Main Results:
- Null mutations in later glycosyltransferase genes cause milder phenotypes.
- Glycan structures modulate glycoprotein localization, half-life, and activity.
- Pathologies in cancer and diabetes-induced cardiac hypertrophy are linked to GlcNAc-T expression.
Conclusions:
- Glycan structures are critical modulators of glycoprotein function.
- Targeting GlcNAc-Ts may offer therapeutic benefits for cancer and diabetes-related conditions.
- Further research into glycosylation pathways can reveal novel therapeutic strategies.