PXD071066

PXD071066 is an original dataset announced via ProteomeXchange.

Title	Galectin-3 binds isoform- and glycoform-specific lacritin in tear fluid
Description	Galectin-3 (Gal-3) is a carbohydrate-binding protein which plays crucial roles in inflammation, immune response, cell migration, autophagy, and signaling. At the ocular surface, Gal-3 is also known to crosslink transmembrane mucins across the epithelial cell glycocalyx, forming lattice structures important for barrier function. However, the biological role of Gal-3 in circulating tear fluid remains largely unexplored. Similarly, whether Gal-3 engages extracellular glycoproteins in tears to affect downstream biological processes has yet to be investigated. As increased Gal-3 levels in tears are known to correlate with ocular pathologies such as dry eye disease (DED), we sought to elucidate the Gal-3 interactome in tear fluid and uncover biological insights into the function of Gal-3 beyond adhesion to the epithelial cell surface. Here, we combined ELISA, lectin affinity enrichment, mass spectrometry (MS) glycoproteomics, and lectin blotting to uncover Gal-3 interactors and their associated glycoepitopes. Overall, we report nearly 100 proteins enriched from tear fluid across 3 different patients, identifying proteins involved in immune response, inflammation, and antimicrobial activity. Most notably, we report lacritin as a novel ligand for Gal-3 and demonstrate that specific glycoforms of lacritin bearing core 2 O-glycans preferentially engage with Gal-3. Lastly, we show that the Gal-3-lacritin axis is spliceoform-specific and dependent on lacritin multimerization. Taken together, this study elucidates new ligands for Gal-3 in tear film and reveals mRNA splicing and multimerization as new biochemical mechanisms which fine-tune Gal-3 binding events.
HostingRepository	PRIDE
AnnounceDate	2026-04-22
AnnouncementXML	Submission_2026-04-22_09:51:28.149.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vincent Chang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	complex glycosylation
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-21 18:17:44	ID requested
⏵ 1	2026-04-22 09:51:28	announced

10.1101/2025.11.24.690288;

submitter keyword: LC-MS/MS, Galectin-3, tear fluid

Stacy Malaker
contact affiliation	Yale University
contact email	stacy.malaker@yale.edu
lab head
Vincent Chang
contact affiliation	Yale University
contact email	vincent.chang@yale.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD071066
     1. Label: PRIDE project
     2. Name: Galectin-3 binds isoform- and glycoform-specific lacritin in tear fluid