{"doi":"10.1101/2023.09.06.556449","title":"Phosphatidylserine clustering by membrane receptors triggers LC3-associated phagocytosis","abstract":"LC3-associated phagocytosis (LAP) represents a non-canonical function of autophagy proteins in which ATG8 family proteins (LC3 and GABARAP proteins) are lipidated onto single-membrane phagosomes as particles are engulfed by phagocytic cells 1–4 . LAP plays roles in innate immunity 5 , inflammation and anti-cancer 6 responses and is initiated upon phagocytosis of particles that stimulate Toll-like receptors (TLR), Fc-receptors, and upon engulfment of dying cells 6 . However, how this molecular route is initiated remains elusive. Here we report that receptors that engage LAP enrich phosphatidylserine (PS) in the phagosome membrane via membrane-proximal domains that are necessary and sufficient for LAP to proceed. Subsequently, PS recruits the Rubicon-containing PI3-kinase complex to initiate the enzymatic cascade leading to LAP. Manipulation of plasma membrane PS content, PS-binding by Rubicon, or the PS-clustering domains of receptors prevents LAP and phagosome maturation. We found that pharmacologic inhibition of PS clustering promotes the ability of dendritic cells to induce anti-cancer responses to engulfed tumor cells. Therefore, the initiation of LAP represents a novel mechanism of PS-mediated signal transduction upon ligation of surface receptors.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":397222,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":243966,"name":"Clifford S. Guy","orcid":null,"position":1,"is_corresponding":false},{"id":1172814,"name":"Gustavo Palacios","orcid":"0009-0001-2483-3774","position":2,"is_corresponding":false},{"id":252502,"name":"Luigi Mari","orcid":"0000-0002-2903-7689","position":3,"is_corresponding":false},{"id":263208,"name":"Zhenrui Li","orcid":"0000-0001-7172-7643","position":4,"is_corresponding":false},{"id":225738,"name":"Douglas R. Green","orcid":"0000-0002-7332-1417","position":5,"is_corresponding":false},{"id":273878,"name":"Emilio Boada-Romero","orcid":"0000-0003-2482-076X","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T01:19:35.497854Z","pmid":null,"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":[]}