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

Autor: Zheng W; Princess Margaret Cancer Center and Department of Medical Biophysics, University of Toronto, Toronto M5G 2M9, Canada., Umitsu M; Princess Margaret Cancer Center and Department of Medical Biophysics, University of Toronto, Toronto M5G 2M9, Canada., Jagan I; Princess Margaret Cancer Center and Department of Medical Biophysics, University of Toronto, Toronto M5G 2M9, Canada.; Cancer Research Institute, Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, Massachusetts 02115, USA., Tran CW; Princess Margaret Cancer Center and Department of Medical Biophysics, University of Toronto, Toronto M5G 2M9, Canada.; Department of Immunology, University of Toronto, Toronto M5S 1A8, Canada., Ishiyama N; Princess Margaret Cancer Center and Department of Medical Biophysics, University of Toronto, Toronto M5G 2M9, Canada., BeGora M; Princess Margaret Cancer Center and Department of Medical Biophysics, University of Toronto, Toronto M5G 2M9, Canada., Araki K; Princess Margaret Cancer Center and Department of Medical Biophysics, University of Toronto, Toronto M5G 2M9, Canada., Ohashi PS; Princess Margaret Cancer Center and Department of Medical Biophysics, University of Toronto, Toronto M5G 2M9, Canada.; Department of Immunology, University of Toronto, Toronto M5S 1A8, Canada., Ikura M; Princess Margaret Cancer Center and Department of Medical Biophysics, University of Toronto, Toronto M5G 2M9, Canada., Muthuswamy SK; Princess Margaret Cancer Center and Department of Medical Biophysics, University of Toronto, Toronto M5G 2M9, Canada.; Cancer Research Institute, Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, Massachusetts 02115, USA.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2016 Nov; Vol. 18 (11), pp. 1244-1252. Date of Electronic Publication: 2016 Oct 03.
DOI: 10.1038/ncb3413
Abstrakt: 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.
Databáze: MEDLINE
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