Hou Lifei, Hsu Alan, Luo Hongbo, Yuki Koichi
Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, Boston, USA.
Department of Anaesthesia and Immunology, Harvard Medical School, Boston, USA.
Eur J Immunol. 2025 Feb;55(2):e202451349. doi: 10.1002/eji.202451349.
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.
含IQ模体的GTP酶激活蛋白1(IQGAP1)是一种整合调节多种细胞功能信号的蛋白质支架。最近,我们利用蛋白质组学作为发现工具,并以免疫共沉淀作为验证方法,报道了IQGAP1作为CD11c的潜在配体,CD11c是一种在中性粒细胞细胞内成分中高度表达的黏附分子,可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尚不清楚。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,我们使用IQGAP1基因敲除(KO)小鼠研究了IQGAP1在中性粒细胞功能中的作用。我们发现IQGAP1缺陷导致骨髓中性粒细胞成熟、活性氧(ROS)生成、吞噬作用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。