the chemotactic defect in wiskott-aldrich syndrome macrophages is due to the reduced persistence of directional protrusionswiskott-aldrich综合症巨噬细胞的趋化现象的缺陷是由于定向突起的持久性.pdfVIP

The Chemotactic Defect in Wiskott-Aldrich Syndrome Macrophages Is Due to the Reduced Persistence of Directional Protrusions 1 1 1 2 1,2 Dan Ishihara , Athanassios Dovas , Haein Park , Beth M. Isaac , Dianne Cox * 1 Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America, 2 Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America Abstract Wiskott-Aldrich syndrome protein (WASp) is an actin nucleation promoting factor that is required for macrophages to directionally migrate towards various chemoattractants. The chemotaxis defect of WASp-deficient cells and its activation by Cdc42 in vivo suggest that WASp plays a role in directional sensing, however, its precise role in macrophage chemotaxis is still unclear. Using shRNA-mediated downregulation of WASp in the murine monocyte/macrophage cell line RAW/LR5 (shWASp), we found that WASp was responsible for the initial wave of actin polymerization in response to global stimulation with CSF-1, which in Dictyostelium discoideum amoebae and carcinoma cells has been correlated with the ability to migrate towards chemoattractants. Real-time monitoring of shWASp cells, as well as WASp2/ 2 bone marrow-derived macrophages (BMMs), in response to a CSF-1 gradient revealed that the protrusions from WASp-deficient cells were directional, showing intact directional sensing. However, the protrusions from WASp-deficient cells demonstrated reduced persistence compared to their respective control shRNA and wild-type cells. Further examination showed that tyro