ArticleInvestigative ophthalmology & visual science2013
Tissue transglutaminase is a negative regulator of monomeric lacritin bioactivity.
Article in Investigative ophthalmology & visual science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 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
- Lacritin cleavage-potentiated targeting of iron - respiratory reciprocity promotes bacterial death.The Journal of biological chemistry · 2025Article
- Targeting Iron - Respiratory Reciprocity Promotes Bacterial Death.bioRxiv : the preprint server for biology · 2024Article
- Mass Spectrometric Identification of a Novel Factor XIIIa Cross-Linking Site in Fibrinogen.Proteomes · 2021Article
- The Role of Endogenous Antimicrobial Peptides in Modulating Innate Immunity of the Ocular Surface in Dry Eye Diseases.International journal of molecular sciences · 2021Review
- Biosynthesized Multivalent Lacritin Peptides Stimulate Exosome Production in Human Corneal Epithelium.International journal of molecular sciences · 2020Article
- Development of a Quantitative Immunoassay for Tear Lacritin Proteoforms.Translational vision science & technology · 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
- Reduced Levels of Tear Lacritin Are Associated With Corneal Neuropathy in Patients With the Ocular Component of Sjögren's Syndrome.Investigative ophthalmology & visual science · 2016Article
- Lacritin and other autophagy associated proteins in ocular surface health.Experimental eye research · 2016Review
- A thermo-responsive protein treatment for dry eyes.Journal of controlled release : official journal of the Controlled Release Society · 2015Article
- A cleavage-potentiated fragment of tear lacritin is bactericidal.The Journal of biological chemistry · 2014Article
- Topical administration of lacritin is a novel therapy for aqueous-deficient dry eye disease.Investigative ophthalmology & visual science · 2014Article
- Lacritin and the tear proteome as natural replacement therapy for dry eye.Experimental eye research · 2013Review
- Lacritin rescues stressed epithelia via rapid forkhead box O3 (FOXO3)-associated autophagy that restores metabolism.The Journal of biological chemistry · 2013Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeMolar accounting of bioactive fluids can expose new regulatory mechanisms in the growing proteomic focus on epithelial biology. Essential for the viability of the surface epithelium of the eye and for normal vision is the thin, but protein-rich, tear film in which the small tear glycoprotein lacritin appears to play a prominent prosecretory, cytoprotective, and mitogenic role. Although optimal bioactive levels in cell culture are 1 to 10 nM over a biphasic dose optimum, ELISA suggests a sustained tear lacritin concentration in the midmicromolar range in healthy adults. Here we identify a reconciling mechanism.
methodsMonoclonal anti-lacritin 1F5 antibody was generated, and applied together with a new anti-C-terminal polyclonal antibody to tear and tissue Western blotting. In vitro tissue transglutaminase (Tgm2) cross-linking was monitored and characterized by mass spectrometry.
resultsBlotting for lacritin in human tears or saliva surprisingly detected immunoreactive material with a higher molecular weight and prominence equal or exceeding the ∼23 to 25 kDa band of monomeric glycosylated lacritin. Exogenous Tgm2 initiated lacritin cross-linking within 1 minute and was complete by 90 minutes-even with as little as 0.1 nM lacritin, and involved the donors lysine 82 and 85 and the acceptor glutamine 106 in the syndecan-1 binding domain. Lacritin spiked into lacritin-depleted tears formed multimers, in keeping with ∼0.6 μM TGM2 in tears. Cross-linking was absent when Tgm2 was inactive, and cross-linked lacritin, unlike recombinant monomer, bound syndecan-1 poorly.
conclusionsSince syndecan-1 binding is necessary for lacritin mitogenic and cytoprotective activities, TGM2 cross-linking negatively regulates lacritin bioactivity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.