{"doi":"10.1016/j.celrep.2020.107973","title":"GSK3 Inhibits Macropinocytosis and Lysosomal Activity through the Wnt Destruction Complex Machinery","abstract":"Canonical Wnt signaling is emerging as a major regulator of endocytosis. Here, we report that Wnt-induced macropinocytosis is regulated through glycogen synthase kinase 3 (GSK3) and the β-catenin destruction complex. We find that mutation of Axin1, a tumor suppressor and component of the destruction complex, results in the activation of macropinocytosis. Surprisingly, inhibition of GSK3 by lithium chloride (LiCl), CHIR99021, or dominant-negative GSK3 triggers macropinocytosis. GSK3 inhibition causes a rapid increase in acidic endolysosomes that is independent of new protein synthesis. GSK3 inhibition or Axin1 mutation increases lysosomal activity, which can be followed with tracers of active cathepsin D, β-glucosidase, and ovalbumin degradation. Microinjection of LiCl into the blastula cavity of Xenopus embryos causes a striking increase in dextran macropinocytosis. The effects of GSK3 inhibition on protein degradation in endolysosomes are blocked by the macropinocytosis inhibitors EIPA or IPA-3, suggesting that increases in membrane trafficking drive lysosomal activity.","journal":"Cell Reports","year":2020,"id":57321,"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":79,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9613,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":299023,"name":"Nydia Tejeda‐Muñoz","orcid":"0000-0001-8314-412X","position":1,"is_corresponding":false},{"id":300359,"name":"Maggie H. Bui","orcid":null,"position":2,"is_corresponding":false},{"id":299024,"name":"Andrew C. Cicchetto","orcid":"0000-0002-5031-3449","position":3,"is_corresponding":false},{"id":299025,"name":"Daniele Di Biagio","orcid":"0000-0002-0773-2170","position":4,"is_corresponding":false},{"id":299026,"name":"Gabriele Colozza","orcid":"0000-0003-4517-3389","position":5,"is_corresponding":false},{"id":299027,"name":"E. Schmid","orcid":"0000-0002-4662-5298","position":6,"is_corresponding":false},{"id":65538,"name":"Stefano Piccolo","orcid":"0000-0002-1600-3092","position":7,"is_corresponding":false},{"id":296410,"name":"Heather R. Christofk","orcid":"0000-0002-8662-4425","position":8,"is_corresponding":false},{"id":299028,"name":"Edward M. De Robertis","orcid":"0000-0002-7843-1869","position":9,"is_corresponding":false},{"id":299022,"name":"Lauren V. Albrecht","orcid":"0000-0002-3147-8010","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-18T21:06:31.136481Z","pmid":"32726636","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":[]}