Protein caught in the act

Researchers have developed a new way to see where the molecules are active

Researchers have illuminated a once-hidden developmental process. A fluorescent signal pinpoints the activity of a protein in fruit flies, allowing researchers to see exactly when and where this protein does its job.

PROTEIN ILLUMINATED. A bioprobe to lights up the activity of a Cdc42 protein in the nervous system of a developing fruit fly embryo. The technique allows researchers to see exactly where and when the protein is active.  IMAGE: Science/AAAS

In certain fruit fly tissues, the protein Cdc42 is more active 15 hours after the embryo is formed than 11 hours after formation. Red indicates high activity, and blue indicates low activity. The yolk — indicated by a dotted outline — glows pink and white in some of these images, even without protein activation. Kamiyama and Chiba, Science/AAAS, 2009

“The idea of watching life at the molecular level within a cell in an intact organism is really fascinating,” says study coauthor Akira Chiba.

The protein, called Cdc42, is present everywhere in the developing fruit fly and controls the production of genes, among other things. But Cdc42 is only active at certain times in certain cells. Chiba and Daichi Kamiyama, both of the University of Miami in Coral Gables, Fla., inserted a gene into the fly’s DNA that encoded an activation bioprobe, an artificial element that sensed when Cdc42’s shape changed, a hallmark of the protein’s activity. This shape change caused the bioprobe to change colors, the researchers report in the June 5 Science.

The pattern of rainbow colors revealed what the researchers call a “surprisingly restricted” pattern of Cdc42 activity. Although the protein was present everywhere, only at specific times during development was it active in the nervous system and in the respiratory system.

Next, the researchers are trying to make activation bioprobes that would work with other proteins. Any protein that changes shapes as it gets activated — a common occurrence — is a candidate for a bioprobe, Chiba says.

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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