{"title":"IQGAP1 Influences Neutrophil Maturation and Its Effector Functions","authors":"Lifei Hou, Alan Hsu, Hongbo Luo, Koichi Yuki","doi":"10.1002/eji.202451349","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>IQ motif containing GTPase activating protein 1 (IQGAP1) is a protein scaffold that integrates signals regulating various cellular functions. Recently, utilizing proteomics as a discovery tool and co-immunoprecipitation as a validation method, we reported IQGAP1 as a potential ligand for CD11c, an adhesion molecule that was highly expressed in the intracellular components of neutrophils and regulated the maturation, survival, and function of neutrophils. To date, the role of IQGAP1 in inflammation and immune response is largely unknown. In this study, we reported the direct binding of CD11c with IQGAP1 through various methods. In addition, we investigated the role of IQGAP1 in neutrophil functions by using IQGAP1 knockout (KO) mice. We discovered that IQGAP1 deficiency led to impaired bone marrow neutrophil maturation, reactive oxygen species (ROS) generation, phagocytosis, and neutrophil extracellular traps formation. Thus, for the first time, we reported the essential role of IQGAP1 in neutrophil development.</p>\n </div>","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"55 2","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Immunology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/eji.202451349","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
IQ motif containing GTPase activating protein 1 (IQGAP1) is a protein scaffold that integrates signals regulating various cellular functions. Recently, utilizing proteomics as a discovery tool and co-immunoprecipitation as a validation method, we reported IQGAP1 as a potential ligand for CD11c, an adhesion molecule that was highly expressed in the intracellular components of neutrophils and regulated the maturation, survival, and function of neutrophils. To date, the role of IQGAP1 in inflammation and immune response is largely unknown. In this study, we reported the direct binding of CD11c with IQGAP1 through various methods. In addition, we investigated the role of IQGAP1 in neutrophil functions by using IQGAP1 knockout (KO) mice. We discovered that IQGAP1 deficiency led to impaired bone marrow neutrophil maturation, reactive oxygen species (ROS) generation, phagocytosis, and neutrophil extracellular traps formation. Thus, for the first time, we reported the essential role of IQGAP1 in neutrophil development.
IQ motif包含GTPase activation protein 1 (IQGAP1),是一种整合调节多种细胞功能的信号的蛋白质支架。最近,利用蛋白质组学作为发现工具和共免疫沉淀作为验证方法,我们报道了IQGAP1作为CD11c的潜在配体,CD11c是一种粘附分子,在中性粒细胞的细胞内成分中高度表达,并调节中性粒细胞的成熟、存活和功能。迄今为止,IQGAP1在炎症和免疫反应中的作用在很大程度上是未知的。在本研究中,我们通过多种方法报道了CD11c与IQGAP1的直接结合。此外,我们利用IQGAP1敲除(KO)小鼠研究了IQGAP1在中性粒细胞功能中的作用。我们发现IQGAP1缺乏导致骨髓中性粒细胞成熟、活性氧(ROS)生成、吞噬和中性粒细胞胞外陷阱形成受损。因此,我们首次报道了IQGAP1在中性粒细胞发育中的重要作用。
期刊介绍:
The European Journal of Immunology (EJI) is an official journal of EFIS. Established in 1971, EJI continues to serve the needs of the global immunology community covering basic, translational and clinical research, ranging from adaptive and innate immunity through to vaccines and immunotherapy, cancer, autoimmunity, allergy and more. Mechanistic insights and thought-provoking immunological findings are of interest, as are studies using the latest omics technologies. We offer fast track review for competitive situations, including recently scooped papers, format free submission, transparent and fair peer review and more as detailed in our policies.