In particular, Wu and Fuchs, who is also a Howard Hughes Medical Institute investigator and Rebecca C. Lancefield Professor at Rockefeller, found that without ACF7, microtubules were no longer guided toward the focal adhesions in a directed manner. They also noticed that cellular movement slowed, suggesting that the sticky adhesive sites were no longer assembling and disassembling efficiently.
To figure out why, Fuchs and Wu studied how quickly wounds heal in mice. "During injury, stem cells proliferate and migrate to the affected site and replenish lost cells," explains Wu. "We saw that the cells without ACF7 proliferated normally, but they moved very, very slowly compared to normal skin cells. So the problem wasn't with abnormal proliferation but with cell migration." When the researchers mutated ACF7 so it couldn't release stored energy in cells, ACF7 linked f-actin and microtubules but the cells were also sluggish in their movement.
In previous work, the Fuchs team had already showed that ACF7 appeared side by side with focal adhesion molecules, but they never knew, until now, that ACF7 guides microtubules along actin cables to these sites. "Now, we have a better idea of why it's important for ACF7 to be there," says Fuchs. "In order to make the adhesive sites dynamically stick and unstick, assembly and disassembly factors need to be recruited there. The intracellular roadway governed by ACF7 makes that possible."
In the future, this information could be relevant in developing cancer therapeutics. "A major goal in the clinical arena is to halt cancer cells from migrating, a process important in metastasis," says Fuchs. By suppressing ACF7's function in cancer cells, it might be possible to slow metastasis.
|Contact: Thania Benios|