{"doi":"10.1016/j.celrep.2023.112726","title":"Cytosolic LPS-induced caspase-11 oligomerization and activation is regulated by extended synaptotagmin 1","abstract":"Caspase-11 (Casp-11) is known to induce pyroptosis and defends against cytosol-invading bacterial pathogens, but its regulation remains poorly defined. Here, we identified extended synaptotagmin 1 (E-Syt1), an endoplasmic reticulum protein, as a key regulator of Casp-11 oligomerization and activation. Macrophages lacking E-Syt1 exhibited reduced production of interleukin-1β (IL-1β) and impaired pyroptosis upon cytosolic lipopolysaccharide (LPS) delivery and cytosol-invasive bacterial infection. Moreover, cleavage of Casp-11 and its downstream substrate gasdermin D were significantly diminished in ESyt1 −/− macrophages. Upon LPS stimulation, E-Syt1 underwent oligomerization and bound to the p30 domain of Casp-11 via its synaptotagmin-like mitochondrial lipid-binding protein (SMP) domain. E-Syt1 oligomerization and its interaction with Casp-11 facilitated Casp-11 oligomerization and activation. Notably, ESyt1 −/− mice were susceptible to infection by cytosol-invading bacteria Burkholderia thailandensis while being resistant to LPS-induced endotoxemia. These findings collectively suggest that E-Syt1 may serve as a platform for Casp-11 oligomerization and activation upon cytosolic LPS sensing.","journal":"Cell Reports","year":2023,"id":330569,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"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":1054786,"name":"Ru Zhao","orcid":null,"position":1,"is_corresponding":false},{"id":52190,"name":"Hui Guo","orcid":"0000-0001-7830-8564","position":2,"is_corresponding":false},{"id":1054787,"name":"Qingchao Tong","orcid":null,"position":3,"is_corresponding":false},{"id":672612,"name":"Wallace Y. Langdon","orcid":"0000-0001-7783-4423","position":4,"is_corresponding":false},{"id":346025,"name":"Weiwei Liu","orcid":"0000-0002-9035-0359","position":5,"is_corresponding":false},{"id":48964,"name":"Jun Zhang","orcid":"0000-0001-6111-670X","position":6,"is_corresponding":false},{"id":471688,"name":"Jian Zhang","orcid":"0000-0001-7217-0111","position":7,"is_corresponding":false},{"id":957361,"name":"Yilei Ma","orcid":null,"position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T01:09:10.120703Z","pmid":"37393619","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":[]}