ArticleProceedings of the National Academy of Sciences of the United States of America2021
Galectin-3 N-terminal tail prolines modulate cell activity and glycan-mediated oligomerization/phase separation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 64 citations in OpenAlex.
- Berbamine hydrochloride as a brain-penetrant galectin-3 inhibitor in a model of Huntington's disease.Brain : a journal of neurology · 2026Article
- Glycoprotein-induced phase separation drives unconventional secretion of galectin-3.Nature communications · 2026Article
- Decoding Galectin-Glycan Recognition withJournal of the American Chemical Society · 2026Article
- Expression, Localization and Actions of Galectin-3: Implications in the Pathophysiology and Therapy of Cardiovascular Disease.International journal of molecular sciences · 2026Review
- Developing Galectin-3-Targeted Therapeutics in Diseases: Three Distinct Galectin-3 Segments for Targeting.Expert reviews in molecular medicine · 2026Review
- Glycobiology-driven therapeutic targeting of glycan-binding proteins: mechanisms, diseases, and clinical translation.Signal transduction and targeted therapy · 2026Review
- Exploring the Interactive Effect of Pectins fromACS omega · 2026Article
- The Historiography of Galactose and Its Recognition by Galectins.Advances in experimental medicine and biology · 2026Review
- Article
- Galectin-3 directs mitophagy in response to Parkin-/proteasome-dependent rupture of mitochondrial outer membrane.Biology direct · 2025Article
- Spatial N-glycan rearrangement on αNature communications · 2025Article
- Chimerolectins: Classification, structural architecture, and functional perspectives.Protein science : a publication of the Protein Society · 2025Review
- Sense, plug, and seal: proteins as both rapid responders and constitutive barriers supporting organelle compartmentalization.Molecular biology of the cell · 2025Review
- hnRNPL phase separation activates PIK3CB transcription and promotes glycolysis in ovarian cancer.Nature communications · 2025Article
- Multifaceted roles of Galectins: from carbohydrate binding to targeted cancer therapy.Biomarker research · 2025Review
- Galectin-3 disrupts tight junctions of airway epithelial cell monolayers by inducing expression and release of matrix metalloproteinases upon influenza A infection.Glycobiology · 2025Article
- Evolution and function of galectins inBBA advances · 2025Article
- Mammalian cell-based production of glycans, glycopeptides and glycomodules.Nature communications · 2024Article
- A Few Charged Residues in Galectin-3's Folded and Disordered Regions Regulate Phase Separation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Exploration into Galectin-3 Driven Endocytosis and Lattices.Biomolecules · 2024Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Galectin-3 (Gal-3) has a long, aperiodic, and dynamic proline-rich N-terminal tail (NT). The functional role of the NT with its numerous prolines has remained enigmatic since its discovery. To provide some resolution to this puzzle, we individually mutated all 14 NT prolines over the first 68 residues and assessed their effects on various Gal-3-mediated functions. Our findings show that mutation of any single proline (especially P37A, P55A, P60A, P64A/H, and P67A) dramatically and differentially inhibits Gal-3-mediated cellular activities (i.e., cell migration, activation, endocytosis, and hemagglutination). For mechanistic insight, we investigated the role of prolines in mediating Gal-3 oligomerization, a fundamental process required for these cell activities. We showed that Gal-3 oligomerization triggered by binding to glycoproteins is a dynamic process analogous to liquid-liquid phase separation (LLPS). The composition of these heterooligomers is dependent on the concentration of Gal-3 as well as on the concentration and type of glycoprotein. LLPS-like Gal-3 oligomerization/condensation was also observed on the plasma membrane and disrupted endomembranes. Molecular- and cell-based assays indicate that glycan binding-triggered Gal-3 LLPS (or LLPS-like) is driven mainly by dynamic intermolecular interactions between the Gal-3 NT and the carbohydrate recognition domain (CRD) F-face, although NT-NT interactions appear to contribute to a lesser extent. Mutation of each proline within the NT differentially controls NT-CRD interactions, consequently affecting glycan binding, LLPS, and cellular activities. Our results unveil the role of proline polymorphisms (e.g., at P64) associated with many diseases and suggest that the function of glycosylated cell surface receptors is dynamically regulated by Gal-3.
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