MLCK stops cells from going full frontal

Myosin light chain kinase (MLCK) controls the number of protrusions extended by crawling cells, Lou et al. report.

Migrating cells polarize to form a protrusive front end. Previous studies have found that Rho GTPases and membrane tension prevent other parts of the cell from forming protrusions. Lou et al. investigated the polarization of zebrafish keratocytes, a type of skin cell. Researchers often study migration mechanisms in keratocytes of other fish species, but zebrafish offer several advantages, including a sequenced genome and techniques for gene knockdown.

Cells from two-day-old embryos were fan shaped, with one large protrusion at the front end. But Lou et al. noticed that cells from four-day-old embryos often sported multiple protrusions. The difference affected the cells’ movement. Keratocytes from two-day-old embryos crawled swiftly, but cells from four-day-old embryos rotated in place like pinwheels.

The researchers found that the activity of MLCK increased in keratocytes from four-day-old embryos. When the researchers inhibited MLCK, these cells extended only a single protrusion. Keratocytes from four-day-old embryos tended to have smaller protrusions than cells from younger embryos. Lou et al. determined that MLCK shrinks these protrusions and shortens their lifetime, thus allowing the cells to generate more of them. MLCK works by inducing myosin to gather in the extensions, causing them to retract. The team found that Rho kinase (ROCK), another molecule that regulates the number of protrusions, played a complementary role, mainly affecting myosin accumulation at the cell’s rear end.