{"doi":"10.1101/2024.01.03.574113","title":"A Genome-Wide CRISPR Screen Identifies Sortilin as the Receptor Responsible for Galectin-1 Lysosomal Trafficking","abstract":"Galectins are a family of mammalian glycan-binding proteins that have been implicated as regulators of myriad cellular processes including cell migration, apoptosis, and immune modulation. Several members of this family, such as galectin-1, exhibit both cell-surface and intracellular functions. Interestingly, galectin-1 can be found in the endomembrane system, nucleus, or cytosol, as well as on the cell surface. The mechanisms by which galectin-1 traffics between cellular compartments, including its unconventional secretion and internalization processes, are poorly understood. Here, we determined the pathways by which exogenous galectin-1 enters cells and explored its capacity as a delivery vehicle for protein and siRNA therapeutics. We used a galectin-1-toxin conjugate, modelled on antibody-drug conjugates, as a selection tool in a genome-wide CRISPR screen. We discovered that galectin-1 interacts with the endosome-lysosome trafficking receptor sortilin in a glycan-dependent manner, which regulates galectin-1 trafficking to the lysosome. Further, we show that this pathway can be exploited for delivery of a functional siRNA. This study sheds light on the mechanisms by which galectin-1 is internalized by cells and suggests a new strategy for intracellular drug delivery via galectin-1 conjugation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":486527,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":830263,"name":"Roarke A. Kamber","orcid":"0000-0001-8462-4782","position":1,"is_corresponding":false},{"id":218281,"name":"Simon Wisnovsky","orcid":"0000-0003-4010-4309","position":2,"is_corresponding":false},{"id":298234,"name":"David S. Roberts","orcid":"0000-0002-0478-4987","position":3,"is_corresponding":false},{"id":1141763,"name":"Egan L. Peltan","orcid":null,"position":4,"is_corresponding":false},{"id":62612,"name":"Michael C. Bassik","orcid":"0000-0001-5185-8427","position":5,"is_corresponding":false},{"id":218284,"name":"Carolyn R. Bertozzi","orcid":"0000-0003-4482-2754","position":6,"is_corresponding":false},{"id":1330789,"name":"Justin Donnelly","orcid":null,"position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T02:08:01.404471Z","pmid":"38260508","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}