In a paper just published in the journal Cell, a team from the University of North Carolina at Chapel1 Hill has explained for the first time how a long-studied protein complex affects cell migration2 and how external cues affect cell's ability to migrate. Cell migration is one of life's basic processes, from development in the womb to immune system response, to learning and brain development, wound healing and -- when it goes wrong -- in cancer.
Jim Bear, PhD, principal investigator3 on the study, says, "The ARP 2/3 protein complex is -- evolutionarily speaking -- very old, but very little is known about what happens to cells when it is eliminated. It was thought previously4 that cells could simply not survive without it. Thanks to Norman Sharpless' lab here at UNC, we were able to find a cell line where the protein can be eliminated without loss of viability5 in order to see what happens to cells."
The result, says Bear, was fascinating. With the ARP 2/3 protein complex intact, cells migrate by forming a fan-shaped structure, called a lamellipodia(板状伪足) , at the leading edge. The team found that eliminating this protein complex caused cells to switch to making finger-shaped protrusions instead -- called filopodia(丝状伪足) . The cells with "fingers" on the leading edge move much more slowly than those with "fans."
Bear, who is an associate professor of cell and developmental biology and a Howard Hughes Medical Institute Early Career Scientist, has focused his laboratory's work around how cell movement responds to environmental cues. Once his team figured out that loss of ARP 2/3 could change cells actual structure and movement, they went on to look at how those changes affected6 the ability of cells to respond to external cues.
"Cells sense a wide variety of soluble7 chemical cues through 'chemotaxis' -- a process that is the basis behind many drugs that target cell behavior. They also respond to attached cues from the surface that they are crawling upon -- a much less well understood process called haptotaxis," says Bear, who is also a member of UNC Lineberger Comprehensive Cancer Center.
So Bear's team set out to test the widely held idea that the cells require lamellipodia "fans" to respond to chemotactic cues. They found that cells with lamellipodia "fans" and filopodia "fingers" (with and without the ARP 2/3 protein complex) respond to chemotaxic cues indistinguishably, although they move faster with lamellipodia.