{"doi":"10.1101/2024.04.01.587559","title":"Regulation of angiogenesis by endocytic trafficking mediated by cytoplasmic dynein 1 light intermediate chain 1","abstract":"ABSTRACT Dynein cytoplasmic 1 light intermediate chain 1 (LIC1, DYNC1LI1 ) is a core subunit of the dynein motor complex. The LIC1 subunit also interacts with various cargo adaptors to regulate Rab-mediated endosomal recycling and lysosomal degradation. Defects in this gene are predicted to alter dynein motor function, Rab binding capabilities, and cytoplasmic cargo trafficking. Here, we have identified a dync1li1 zebrafish mutant, harboring a premature stop codon at the exon 12/13 splice acceptor site, that displays increased angiogenesis. In vitro , LIC1-deficient human endothelial cells display increases in cell surface levels of the pro-angiogenic receptor VEGFR2, SRC phosphorylation, and Rab11-mediated endosomal recycling. In vivo , endothelial-specific expression of constitutively active Rab11a leads to excessive angiogenesis, similar to the dync1li1 mutants. Increased angiogenesis is also evident in zebrafish harboring mutations in rilpl1/2 , the adaptor proteins that promote Rab docking to Lic1 to mediate lysosomal targeting. These findings suggest that LIC1 and the Rab-adaptor proteins RILPL1 and 2 restrict angiogenesis by promoting degradation of VEGFR2-containing recycling endosomes. Disruption of LIC1- and RILPL1/2-mediated lysosomal targeting increases Rab11-mediated recycling endosome activity, promoting excessive SRC signaling and angiogenesis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":496125,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"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":451312,"name":"Sarah Colijn","orcid":"0000-0003-3419-9970","position":1,"is_corresponding":false},{"id":1299072,"name":"Jahmiera Richee","orcid":null,"position":2,"is_corresponding":false},{"id":325863,"name":"Joseph J. Yano","orcid":"0000-0001-7910-5769","position":3,"is_corresponding":false},{"id":107844,"name":"Margaret C. Burns","orcid":"0000-0001-5380-4676","position":4,"is_corresponding":false},{"id":325860,"name":"Andrew Davis","orcid":"0000-0002-8259-3174","position":5,"is_corresponding":false},{"id":325861,"name":"Van N. Pham","orcid":"0009-0005-1065-6649","position":6,"is_corresponding":false},{"id":677063,"name":"Amra Sarić","orcid":"0000-0002-5994-5864","position":7,"is_corresponding":false},{"id":714350,"name":"Akansha Jain","orcid":"0000-0002-0503-8142","position":8,"is_corresponding":false},{"id":1172891,"name":"Ying Yin","orcid":"0000-0001-6553-1644","position":9,"is_corresponding":false},{"id":325862,"name":"Daniel Castranova","orcid":"0000-0002-2845-9708","position":10,"is_corresponding":false},{"id":1298622,"name":"Mariana Melani","orcid":"0000-0002-9491-932X","position":11,"is_corresponding":false},{"id":1298623,"name":"Misato Fujita","orcid":"0000-0002-1034-7759","position":12,"is_corresponding":false},{"id":411224,"name":"Stephanie Grainger","orcid":"0000-0001-6889-7174","position":13,"is_corresponding":false},{"id":62801,"name":"Juan S. Bonifacino","orcid":"0000-0002-5673-6370","position":14,"is_corresponding":false},{"id":301662,"name":"Brant M. Weinstein","orcid":"0000-0003-4136-4962","position":15,"is_corresponding":false},{"id":325858,"name":"Amber N. Stratman","orcid":"0000-0002-8111-4186","position":16,"is_corresponding":false},{"id":1167937,"name":"Dymonn Johnson","orcid":null,"position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-19T02:09:23.333150Z","pmid":"38903077","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":[]}