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Bioinformatics Resources for the Study of Glycan-Mediated Protein Interactions
Published on: January 20, 2022
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Nutrient-responsive O-GlcNAcylation dynamically modulates the secretion of glycan-binding protein galectin 3
Mohit P Mathew1, Lara K Abramowitz1, Julie G Donaldson2
1Laboratory of Cell and Molecular Biology, NIDDK, Bethesda, Maryland, USA.
The Journal of Biological Chemistry
|February 20, 2022
Summary
Dynamic O-GlcNAcylation of galectin 3 controls its secretion and function in nutrient sensing. This process links cell surface glycosylation to biological effects, impacting diseases like cancer and diabetes.
Area of Science:
- Biochemistry
- Cell Biology
- Glycobiology
Background:
- Endomembrane glycosylation and cytoplasmic O-GlcNAcylation are crucial for nutrient sensing, with altered patterns observed in diseases like diabetes and cancer.
- Galectins, glycan-binding proteins, are secreted via a nonclassical pathway and modulate extracellular functions, including clathrin-independent endocytosis (CIE).
- The integration mechanisms of glycosylation and O-GlcNAcylation signaling remain poorly understood.
Purpose of the Study:
- To investigate the role of O-GlcNAcylation in galectin 3 secretion and its impact on cellular functions.
- To elucidate how nutrient-sensing signals are integrated through galectin 3 modulation.
Main Methods:
- Immunoprecipitation and Western blotting were used to assess galectin 3 O-GlcNAcylation status.
- Galectin 3 secretion was monitored under varying nutrient conditions and O-GlcNAc levels.
- Changes in clathrin-independent endocytosis (CIE) were analyzed in relation to galectin 3 secretion.
Main Results:
- Galectin 3 is a substrate for O-GlcNAc transferase, with distinct O-GlcNAcylation states between cytoplasmic and secreted forms.
- Galectin 3 secretion is dynamically regulated by nutrient availability and O-GlcNAc levels.
- O-GlcNAc-dependent alterations in galectin 3 secretion significantly influenced CIE rates.
Conclusions:
- Dynamic O-GlcNAcylation of galectin 3 is a key regulator of its secretion.
- This O-GlcNAcylation mechanism allows galectin 3 to transduce nutrient-sensing information from cell surface glycosylation into biological responses.
- Findings highlight a novel link between nutrient sensing, protein secretion, and cellular function, with implications for disease states.
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