Biologists unravel mechanisms of immune cell movements

Human white blood cells navigate to and destroy bacteria by following a chemical that bacteria secrete. But less well understood are the biochemical processes within these immune cells that allow them to speed their way to bacteria and the sites of wounds and infections, often causing inflammation.

UCSD's Pascale Charest discovered a novel underlying mechanism that helps direct white blood cells to sites of infections.

Now a team of biologists from the University of California, San Diego, led by Richard Firtel, a professor of biology at UCSD, has uncovered a major piece of the puzzle. In the 18 May issue of the journal Developmental Cell, the UCSD scientists report that they discovered a previously unknown complex of proteins that guides amoebae and mammalian immune cells toward their prey.

The team's discoveries were made in Dictyostelium, a simple social amoeba and model genetic system that exhibits many of the properties of human white blood cells. This amoeba is controlled by the same navigation system as mammalian immune cells, but has a much simpler genetic system and can be grown more easily and rapidly in a laboratory than mammalian cells.

Working in collaboration with UCSD biology professor Steven Briggs and Zhouxin Shen, a senior scientist in Briggs' laboratory, Pascale Charest, a post-doctoral fellow in Firtel's UCSD laboratory and the first author of the paper, discovered a large multi-protein complex, called the ''Sca1 complex,'' and found that it controlled the action of another protein called ''Ras,'' known to be important in directing a cell's movements.

Ras connects the cell's direction-sensing compass to its molecular motors, which allows the cell to move toward its targeted prey by making actin in the parts of the cell closest to the food and then taking the actin away from the other ends of the cell. The Sca1 complex acts as a navigator, activating Ras only at the correct spot along the cell's surface and thus defining the direction of cell movement.

This constant extension and contraction of the cell's contents, which occurs over a period of about two minutes, is controlled by Ras and the Sca1 complex, and by another complex of proteins called TORC2, for Target of Rapamycin Complex 2, which helps in the chemical navigation system of the amoeba.