White blood cells, or neutrophils, are the body's first line of defense against potentially harmful microbes, and are one of the swiftest cells in the body. The wave action that speeds them along is generated by the same kind of three-part circuit that fires electrical signals along a neuron or prods the heart to beat, the researchers observe.

Videotaping allowed the scientists to watch as wave upon wave of the Hem-1 protein push neutrophils toward a chemical signal made by invading microbes. The researchers fluorescently tagged Hem-1 to view its dynamic propulsive power under the microscope.

Self-generating waves of Hem-1 control the pattern of assembly of building blocks of a second protein, actin. This protein physically contacts the cell membrane and prods it forward. But actin is not only an output of Hem-1 action; it also appears to eliminate the Hem-1 that has assembled it, the new research shows. The scientists think that this cycle of Hem-1 propulsion and annihilation is likely to produce the series of waves seen under the microscope.

The cell-propelling circuit contains a third component that makes it self-sustaining. The researchers found evidence that before each Hem-1 protein is eliminated, it recruits an additional Hem-1 right "next door." As each Hem-1 succumbs, a new one appears - but only on one side. Weiner thinks the structure of actin physically blocks Hem-1 from recruiting its daughter Hem-1 on one side, so Hem-1 is sequentially added only in one direction. This determines the direction of cell movement.

Weiner likens it to a Lego tower on its side. "If you kept adding blocks to one end and removing them from the other, you would have a moving tower that was the same size but kept adding new material. This is very similar to what is going on in a Hem-1 wave," he says.

The Hem-1 recruitment assures t
'"/>

Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
13-Aug-2007