How migrating cells build their leading edge: Master regulator may resolve long-standing debate

The ability of cells to move and change position is essential for various processes in our bodies. Immune cells move to sites of action, epithelial cells migrate during wound closure, and neurons extend their axons for signal transmission.

By Christian Heinrich, Helmholtz Centre for Infection Research This article has been reviewed according to Science X's editorial process and policies. The results are published in Nature Communications.

Using genome editing by CRISPR/Cas9, the researchers first disrupted various players in the process, alone and in combination. These interactions operate as follows: Profilin counteracts Ena/VASP and at the same time promotes Arp2/3 complex activity.

Combinations of gene disruptions have been particularly informative: Profilin was still crucial for Arp2/3 complex localization even in the absence of Ena/VASP, but this was not seen for CP. The results thus resolve several controversial issues: Previous research has either suggested that profilin funnels actin monomers into formin- or Ena/VASP-dependent actin structures, and thus away from Arp2/3 complex, or supported the opposite view.

We are now clarifying this controversy by clearly showing profilin to operate upstream of Arp2/3 complex in lamellipodia and also how," Rottner says. Martin Falcke from Max Delbrück Center Berlin not only recapitulated all experimental results but also implied that Ena/VASP and CP have to compete for a common recruitment mechanism in lamellipodia.

This mechanistic understanding forms the basis for examining what goes wrong in aberrant migration, ranging from cancer metastasis to cells suffering from infections, and how those processes can potentially be targeted.

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