Experimenting with a simple amoeba, researchers have developed a new fluorescence-based test that could screen candidate compounds for cancer, asthma and heart disease drugs.
When hormones, neurotransmitters or chemical attractors reach a cell, they dock to and activate a membrane-spanning receptor. On the inside of the cell, some of these receptors bind to a so-called G-protein, consisting of three subunits: alpha, beta and gamma. In response to the signal, the G-protein breaks up into two parts, alpha and beta/gamma. Both parts pass the signal on to other molecules in the cell, and ultimately make it move, divide or change its behavior in other ways.
In today's Science, researchers from Johns Hopkins University describe a novel test to determine whether the signal is "on" or "off": they attached different labels to the alpha-part and to the beta/gamma-part of a G-protein from the amoeba Dictyostelium discoideum such that these parts emitted different kinds of light in response to blue light. When all three subunits stayed close together in the "off" state, they emitted yellow fluorescent light. When the two parts were separated in the "on" state, however, the alpha-part emitted blue-green fluorescent light; the beta/gamma part remained dark.
The scientists used this test to study the effects of a certain chemical that attracts the amoeba, a process called chemotaxis that requires G-protein signaling. A recent study in Nature reported that chemotaxis also plays a role in metastasis of cancer cells and that blocking the signal with a drug prevented malignant cells from spreading. In fact, many drugs bind to G-protein coupled receptors, and in mammalian cells, this test could show if they act as agonists (turning the signal on) or antagonists (blocking the signal)."We were doing basic research to study chemotaxis, but it turns out to be useful for medicine," Chris Janetopoulos, the lead author of the study, says. "We think the potential could be huge for the pharmaceutical industry," he adds, and the group is in the process of patenting the technique.