N-WASP has the ability to compensate for the loss of WASP in macrophage podosome formation and chemotaxis |
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Authors: | Beth M Isaac Dan Ishihara Leora M Nusblat Athanassios Dovas |
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Institution: | a Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA b Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA c INSERM U865, Lyon, France |
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Abstract: | Wiskott-Aldrich syndrome protein (WASP) and its homologue neural-WASP (N-WASP) are nucleation promoting factors that integrate receptor signaling with actin cytoskeleton rearrangement. While hematopoietic cells express both WASP and N-WASP, WASP deficiency results in altered cell morphology, loss of podosomes and defective chemotaxis. It was determined that cells from a mouse derived monocyte/macrophage cell line and primary cells of myeloid lineage expressed approximately 15-fold higher levels of WASP relative to N-WASP. To test whether N-WASP can compensate for the loss of WASP and restore actin cytoskeleton integrity, N-WASP was overexpressed in macrophages, in which endogenous WASP expression was reduced by short hairpin RNA (shWASP cells). Many of the defects associated with the loss of WASP, such as podosome-dependent matrix degradation and chemotaxis were corrected when N-WASP was expressed at equimolar level to that of the wild-type WASP. Furthermore, the ability of N-WASP to partially compensate for the loss of WASP may be physiologically relevant since activated murine WASP-deficient peritoneal macrophages, which show enhanced N-WASP expression, also show an increase in matrix degradation. Our study suggests that expression levels of WASP and N-WASP may influence their roles in actin cytoskeleton rearrangement and shed light to the complex intertwining roles WASP and N-WASP play in macrophages. |
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Keywords: | BMM bone marrow-derived macrophages CSF-1 macrophage colony stimulating factor-1 DC dendritic cells GBD G protein binding domain N-WASP Neuronal-Wiskott-Aldrich syndrome protein shRNA Short Hairpin RNA WAS Wiskott-Aldrich syndrome WASP Wiskott-Aldrich syndrome protein WAVE WASP family verproline-homologous protein |
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