Ezrin, radixin, and moesin are dispensable for macrophage migration and cellular cortex mechanics

The cellular cortex provides crucial mechanical support and plays critical roles during cell division and migration. The proteins of the ERM family, comprised of ezrin, radixin, and moesin, are central to these processes by linking the plasma membrane to the actin cytoskeleton. To investigate the contributions of the ERM proteins to leukocyte migration, we generated single and triple ERM knockout macrophages. Surprisingly, we found that even in the absence of ERM proteins, macrophages still form the different actin structures promoting cell migration, such as filopodia, lamellipodia, podosomes, and ruffles. Furthermore, we discovered that, unlike every other cell type previously investigated, the single or triple knockout of ERM proteins does not affect macrophage migration in diverse contexts. Finally, we demonstrated that the loss of ERMs in macrophages does not affect the mechanical properties of their cortex. These findings challenge the notion that ERMs are universally essential for cortex mechanics and cell migration and support the notion that the macrophage cortex may have diverged from that of other cells to allow for their uniquely adaptive cortical plasticity. Ezrin, radixin, and moesin (collectively known as ERM proteins) serve as crucial cytoskeletal linker proteins connecting the actin cytoskeleton to the plasma membrane. This study shows that a complete loss of ERM proteins in macrophages does not affect the mechanics of their actin cortex and their capacity to migrate.Macrophage actin structures are still correctly formed in the absence of ERM proteins.Macrophage migration in vitro, ex vivo and in vivo is not affected by ERM depletion.The mechanical properties of the macrophage cortex are independent of ERM proteins. Macrophages do not require the ERM family proteins for phagocytosis and cell migration, suggesting divergence of macrophage cortical properties.