This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: 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 over long distances.
In metastasis, cancer cells employ their motile machinery to spread throughout the body. Klemens Rottner, who heads the Research Group "Molecular Cell Biology" at the Helmholtz Center for Infection Research (HZI), has shed new light on the central molecular interactions that accompany the formation of cytoskeletal networks at the leading edge of migrating cells. The insights pave the way for defining how such processes change in diseases and how they can potentially be modulated in the future.
The results are published in Nature Communications. Among the most prominent structures driving cell migration are so-called lamellipodia, which are flat and broad and push the cell front forward. Lamellipodia are built of dense networks of polymers mostly comprising the protein actin, and they are dynamically renewed to translate pushing forces into forward movement.
But how are these structures regulated at the molecular scale? "The role of the actin-binding protein profilin in these processes has been controversial, but our results could largely clarify previous inconsistencies in the literature," Rottner says. Using genome editing by CRISPR/Cas9, the researchers first disrupted various players in the process, alone and in combination.
They then explored how this affected the formation and function of lamellipodia, as well as the relative distributions of remaining proteins. They were able to establish the functional connections between the most relevant players in these structures in a stepwise manner, including the roles of four components: "We have succeeded in improving our understanding of how all those lamellipodial components interact with and influence each other—thereby collectively regulating forward movement," Dr. Yubo Tang says, the study's first author.
These interactions operate as follows: Profilin counteracts Ena/VASP and at the same time promotes Arp2/3 complex activity. Ena/VASP and capping protein antagonize each other. 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.
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