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

Nature Cell Biology 18, 1244 (2016).
doi:10.1038/ncb3413

Authors: Weiyue Zheng, Masataka Umitsu, Ishaan Jagan, Charles W. Tran, Noboru Ishiyama, Michael BeGora, Kiyomi Araki, Pamela S. Ohashi, Mitsuhiko Ikura & Senthil K. Muthuswamy
The polarity protein Scribble (SCRIB) regulates apical–basal polarity, directional migration and tumour suppression in Drosophila and mammals. 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.

Source: Nature Cell Biology - October 2, 2016 Category: Cytology Authors: Weiyue Zheng Masataka Umitsu Ishaan Jagan Charles W. Tran Noboru Ishiyama Michael BeGora Kiyomi Araki Pamela S. Ohashi Mitsuhiko Ikura Senthil K. Muthuswamy Tags: Letter Source Type: research