节点2
细胞生物学
泛素
炎症
胞浆
势垒函数
化学
细胞外
功能(生物学)
鸟嘌呤核苷酸交换因子
生物
信号转导
免疫学
基因
生物化学
先天免疫系统
受体
酶
作者
Phi Luong,Matija Hedl,Jie Yan,Tao Zuo,Tian‐Min Fu,Xiaomo Jiang,Jay R. Thiagarajah,Steen Ingemann Hansen,Cammie F. Lesser,Hao Wu,Clara Abraham,Wayne I. Lencer
出处
期刊:eLife
[eLife Sciences Publications, Ltd.]
日期:2018-10-25
卷期号:7
被引量:17
摘要
Homeostasis at mucosal surfaces requires cross-talk between the environment and barrier epithelial cells. Disruption of barrier function typifies mucosal disease. Here we elucidate a bifunctional role in coordinating this cross-talk for the inflammatory bowel disease risk-gene INAVA. Both activities require INAVA's DUF3338 domain (renamed CUPID). CUPID stably binds the cytohesin ARF-GEF ARNO to effect lateral membrane F-actin assembly underlying cell-cell junctions and barrier function. Unexpectedly, when bound to CUPID, ARNO affects F-actin dynamics in the absence of its canonical activity as a guanine nucleotide-exchange factor. Upon exposure to IL-1β, INAVA relocates to form cytosolic puncta, where CUPID amplifies TRAF6-dependent polyubiquitination and inflammatory signaling. In this case, ARNO binding to CUPID negatively-regulates polyubiquitination and the inflammatory response. INAVA and ARNO act similarly in primary human macrophages responding to IL-1β and to NOD2 agonists. Thus, INAVA-CUPID exhibits dual functions, coordinated directly by ARNO, that bridge epithelial barrier function with extracellular signals and inflammation.
科研通智能强力驱动
Strongly Powered by AbleSci AI