The Molecular Pathway for Cell Migration: Navigating Obstacles with Snx33 Protein

Cells in our body often migrate through tissues by extending a leading edge that helps guide their movement. However, when the leading edge encounters an obstacle, such as another cell or physical barrier, the cell needs a mechanism to navigate around it. A recent study by the Diz-Muñoz group at EMBL Heidelberg has identified a novel molecular pathway involving the Snx33 protein that enables cells to overcome obstacles during migration.

The leading edge of a migrating cell is formed by the extension of its outer membrane and cytoplasm in a specific direction. This leading edge is initially dynamic but eventually stabilizes with the help of the cytoskeleton, a network of actin filaments. However, when the leading edge encounters an obstacle, the cell must adjust its course to continue migrating. This is where Snx33, a curvature-sensing protein belonging to the BAR-domain protein family, comes into play.

The researchers found that when a cell encounters an obstacle, the curvature of its leading edge changes. Snx33 senses this change and recruits molecular machinery to inhibit the actin cytoskeleton, allowing the cell to dissolve the leading edge and change direction. Cells lacking Snx33 were slower in navigating crowded or barrier-filled environments.

BAR-domain proteins, including Snx33, are highly conserved in animal cells. The diversity of BAR-domain proteins allows cells to decode and respond to membrane curvature in unique ways, enabling quick and complex reactions to different environmental stimuli. This finding suggests that other migrating cell types, such as tumor cells or embryonic cells, may also use similar mechanisms for navigation.

The study provides impetus for further research on curvature-sensing proteins, as there are more than 80 such proteins in mammalian cells, many of which are still poorly understood. Understanding these proteins and their role in cell migration could have broad implications for various biological processes.

This study highlights the importance of Snx33 as a molecular gatekeeper that tells cells to find an alternative path when faced with an obstacle. The ability to sense curvature and activate downstream pathways may have broader implications at the level of tissues. Further investigations into curvature-sensing proteins will shed light on this vital biological process.

Ewa Sitarska et al. Sensing their plasma membrane curvature allows migrating cells to circumvent obstacles, Nature Communications (2023). DOI: 10.1038/s41467-023-41173-1