An interaction between Scribble and the NADPH oxidase complex controls M1 macrophage polarization and function

作者：Zheng Weiyue; Umitsu Masataka; Jagan Ishaan; Tran Charles W; Ishiyama Noboru; BeGora Michael; Araki Kiyomi; Ohashi Pamela S; Ikura Mitsuhiko; Muthuswamy Senthil K^*

来源：Nature Cell Biology, 2016, 18(11): 1244-+.

DOI：10.1038/ncb3413

The polarity protein Scribble (SCRIB) regulates apical-basal polarity, directional migration and tumour suppression in Drosophila and mammals(1-6). Here we report that SCRIB is an important regulator of myeloid cell functions including bacterial infection and inflammation. SCRIB interacts directly with the NADPH oxidase (NOX) complex in a PSD95/Dlg/ZO-1 (PDZ)-domain-dependent manner and is required for NOX-induced reactive oxygen species (ROS) generation in culture and in vivo. On bacterial infection, SCRIB localized to phagosomes in a leucine-rich repeat-dependent manner and promoted ROS production within phagosomes to kill bacteria. Unexpectedly, SCRIB loss promoted M1 macrophage polarization and inflammation. Thus, SCRIB uncouples ROS-dependent bacterial killing activity from M1 polarization and inflammatory functions of macrophages. Modulating the SCRIB-NOX pathway can therefore identify ways to manage infection and inflammation with implications for chronic inflammatory diseases, sepsis and cancer.

• 出版日期2016-11