The migration of macrophages: a mechanism that deviates from the norm

In an article published in the EMBO Journal, scientists demonstrate that macrophage migration can occur without the ERM proteins, which were previously considered essential for any cell migration. Their results show that specific mechanisms are at work in these key cells of our immune system.

ERM proteins are indispensable for cell migration…
Each cell in our body is separated from its external environment by a membrane known as the plasma membrane. Just beneath this plasma membrane lies the cellular cortex, which gives the cell its shape. The cortex is composed of a dynamic network of actin filaments, allowing the cell to change shape, divide, or move. Among the components of the cortex is the family of ERM proteins, which includes Ezrin, Radixin, and Moesin. These proteins play a central role in all these functions by establishing a mechanical link between the plasma membrane and the actin filaments.

Except in macrophages…
Macrophages are essential for immune response, tissue repair, and, in certain pathological contexts, the worsening of diseases, as demonstrated in many cancers. Therefore, understanding how macrophages move within tissues is crucial for potentially blocking this process when necessary.

In an article published in EMBO Journal, scientists aiming to study the underlying mechanisms of this migration discovered that deleting the three ERM proteins does not disrupt macrophage migration, contrary to the previously thought universal role of ERM proteins in this mechanism.

The scientists generated mutant macrophages in which each ERM protein was individually or simultaneously deleted. These mutant macrophages were created using CRISPR/Cas9 technology in an innovative cellular model, resulting in the first triple ERM mutant. Surprisingly, in the absence of ERMs, the macrophages displayed no migration defects. Furthermore, unlike all other cell types studied previously, the loss of ERMs in macrophages did not affect the mechanics of their cellular cortex. These results challenge the idea that ERMs are universally essential for cortex mechanics and cell migration, suggesting that the macrophage cortex may have diverged from that of other cells to enable adaptive cortical plasticity. Indeed, macrophages are one of the rare cell types present in all body tissues. Thus, it is likely that to achieve this versatility, they possess alternative mechanisms to fulfill functions necessary for organism survival, which remain to be discovered.