ArticleThe Journal of biological chemistry2013
Targeting of heparanase-modified syndecan-1 by prosecretory mitogen lacritin requires conserved core GAGAL plus heparan and chondroitin sulfate as a novel hybrid binding site that enhances selectivity.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
- Site-specific O-glycans influence lacritin structure and multimerization in tears.Protein science : a publication of the Protein Society · 2026Article
- Distinctive Lacritin Cleavage-Potentiated Bactericidal Alteration of thebioRxiv : the preprint server for biology · 2026Article
- Mapping galectin-3 ligands in human tear fluid establishes spliceoform-dependent lacritin binding.Communications biology · 2026Article
- In-depth analysis of the tear fluid glycoproteome reveals diverse lacritin glycosylation and spliceoforms.The Journal of biological chemistry · 2025Article
- In-depth analysis of the tear fluid glycoproteome reveals diverse lacritin glycosylation and spliceoforms.bioRxiv : the preprint server for biology · 2025Article
- Solid-Phase-Supported Chemoenzymatic Synthesis and Analysis of Chondroitin Sulfate Proteoglycan Glycopeptides.Angewandte Chemie (International ed. in English) · 2024Article
- Targeting Iron - Respiratory Reciprocity Promotes Bacterial Death.bioRxiv : the preprint server for biology · 2024Article
- Autophagy in the normal and diseased cornea.Experimental eye research · 2022Review
- Excavating proteoglycan structure-function relationships: modern approaches to capture the interactions of ancient biomolecules.American journal of physiology. Cell physiology · 2022Review
- Chemical editing of proteoglycan architecture.Nature chemical biology · 2022Article
- A heparan-sulfate-bearing syndecan-1 glycoform is a distinct surface marker for intra-tumoral myeloid-derived suppressor cells.iScience · 2021Article
- Selection and structural characterization of anti-TREM2 scFvs that reduce levels of shed ectodomain.Structure (London, England : 1993) · 2021Article
- Biosynthesized Multivalent Lacritin Peptides Stimulate Exosome Production in Human Corneal Epithelium.International journal of molecular sciences · 2020Article
- Downregulation of miR-10a inhibits cutaneous squamous cell carcinoma cell proliferation, migration, and invasion by targeting Syndecan-1.International journal of clinical and experimental pathology · 2020Article
- The Lacritin-Syndecan-1-Heparanase Axis in Dry Eye Disease.Advances in experimental medicine and biology · 2020Review
- TFOS DEWS II Tear Film Report.The ocular surface · 2017Review
- Molecular Functions of Glycoconjugates in Autophagy.Journal of molecular biology · 2016Review
- A Proteoglycan-Like Molecule Offers Insights Into Ground Substance Changes During Holothurian Intestinal Regeneration.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2016Article
- Lacritin and other autophagy associated proteins in ocular surface health.Experimental eye research · 2016Review
- Syndecan-1 and Its Expanding List of Contacts.Advances in wound care · 2015Review
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Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
Abstract
Cell surface heparan sulfate (HS) proteoglycans shape organogenesis and homeostasis by capture and release of morphogens through mechanisms largely thought to exclude the core protein domain. Nevertheless, heparanase deglycanation of the N-terminal HS-rich domain of syndecan-1 (SDC1), but not SDC2 or -4, is a prerequisite for binding of the prosecretory mitogen lacritin (Ma, P., Beck, S. L., Raab, R. W., McKown, R. L., Coffman, G. L., Utani, A., Chirico, W. J., Rapraeger, A. C., and Laurie, G. W. (2006) Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin. J. Cell Biol. 174, 1097-1106). We now report that the conserved and hydrophobic GAGAL domain in SDC1, adjacent to predicted HS substitution sites, is necessary to ligate and substantially enhance the α-helicity of the amphipathic C terminus of lacritin. Swapping out GAGAL for GADED in SDC2 or for GDLDD in SDC4 (both less hydrophobic) abrogated binding. HS and chondroitin sulfate are also essential. Both are detected in the N terminus, and when incubated with antibodies HS4C3 (anti-HS) or IO3H10 (anti-chondroitin sulfate), binding was absent, as occurred when all three N-terminal glycosaminoglycan substitution sites were mutated to alanine or when cells were treated with 4-methylumbelliferyl-β-d-xylopyranoside or chlorate to suppress glycosaminoglycan substitution or sulfation, respectively. SDC1 interacts with the hydrophobic face of lacritin via Leu-108/Leu-109/Phe-112 as well as with Glu-103/Lys-107 and Lys-111 of the largely cationic face. Carving a hybrid hydrophobic/electrostatic docking site out of SDC1 in a manner dependent on endogenous heparanase is a dynamic process appropriate for subtle or broad epithelial regulation in morphogenesis, health, and disease.
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