{"doi":"10.1101/2020.12.22.424011","title":"GPCR-mediated Activation of PLCγ2 Initiates Dysregulated Recruitment of Neutrophils in Cold-induced Urticaria in PLAID Patients","abstract":"Abstract The current dogma is that chemoattractants G protein coupled receptors (GPCRs) activate β phospholipase C (PLCβ) while receptor tyrosine kinases (RTKs) activate γ phospholipase C (PLCγ). Here, we show that chemoattractant/GPCR-mediated membrane recruitment of PLCγ2 constitutes GPCR-mediated phospholipase C (PLC) signaling and is essential for neutrophil polarization and migration during GPCR-mediated chemotaxis. In response to a chemoattractant stimulation, cells lacking PLCγ2 ( plcg2 kd ) displayed altered dynamics of diacylglycerol (DAG) production and calcium response; increased Ras/PI3K/Akt activation; elevated GSK3 phosphorylation and cofilin activation; impaired dynamics of actin polymerization; and consequently defects in cell polarization and migration during chemotaxis. At low temperature, neutrophils expressing the gain-of-function mutant of PLCγ2 (Δ686) displayed better chemotaxis than the cells expressing wild-type PLCγ2. The study provides a molecular mechanism for the dysregulated recruitment and activation of neutrophils in cold-induced urticaria in PLCγ2-associated antibody deficiency and immune dysregulation (PLAID) patients bearing gain-of-function mutations of PLCγ2.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":132080,"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":0.9478,"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":570027,"name":"Xi Wen","orcid":"0000-0002-7103-9936","position":1,"is_corresponding":false},{"id":570029,"name":"Smit Bhimani","orcid":"0000-0001-5549-9994","position":2,"is_corresponding":false},{"id":570028,"name":"Amer Moosa","orcid":"0000-0002-7614-6650","position":3,"is_corresponding":false},{"id":587532,"name":"Dustin Parsons","orcid":null,"position":4,"is_corresponding":false},{"id":430212,"name":"Tian Jin","orcid":"0000-0003-4815-0668","position":5,"is_corresponding":false},{"id":570026,"name":"Xuehua Xu","orcid":"0000-0002-3863-9593","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-18T23:16:07.542484Z","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":[]}