{"doi":"10.1083/jcb.202405174","title":"PILS-Nir1 is a sensitive phosphatidic acid biosensor that reveals mechanisms of lipid production","abstract":"Phosphatidic acid (PA) regulates lipid homeostasis and vesicular trafficking, yet high-affinity tools to study PA in live cells are lacking. We identified the lipin-like sequence of Nir1 (PILS-Nir1) as a candidate PA biosensor based on structural analysis of Nir1's LNS2 domain. Using liposome-binding assays and pharmacological and genetic manipulations in HEK293A cells expressing fluorescent PILS-Nir1, we found that while PILS-Nir1 binds PA and PIP2in vitro, only PA is necessary and sufficient for membrane localization in cells. PILS-Nir1 displayed greater sensitivity to organelle-generated PA than Spo20-based probes, enabling visualization of modest PA production by PLD downstream of muscarinic receptors-previously undetectable with existing biosensors. Thus, PILS-Nir1 provides a versatile, sensitive tool for real-time PA dynamics in live cells.","journal":"The Journal of Cell Biology","year":2025,"id":515979,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9596,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1332542,"name":"T. Rähn","orcid":"0000-0002-5031-6914","position":1,"is_corresponding":false},{"id":1381350,"name":"M. Ehrlich","orcid":null,"position":2,"is_corresponding":false},{"id":278212,"name":"Rachel C. Wills","orcid":"0000-0003-2161-9235","position":3,"is_corresponding":false},{"id":307524,"name":"Joshua G. Pemberton","orcid":"0000-0002-1492-1471","position":4,"is_corresponding":false},{"id":348775,"name":"Michael V. Airola","orcid":"0000-0003-4981-1253","position":5,"is_corresponding":false},{"id":245412,"name":"Gerald Hammond","orcid":"0000-0002-6660-3272","position":6,"is_corresponding":false},{"id":842560,"name":"Claire C. Weckerly","orcid":"0000-0003-2368-8429","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T02:48:44.647022Z","pmid":"40923975","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":[]}