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Fluorescent flicks: Movies capture proteins in action

Scientists have created a new tool—a fluorescent tag—that allows them to track proteins moving inside cells in real time. The tag binds to a protein and glows bright green when exposed to certain wavelengths of light. In a new study, the researchers created movies of the fluorescent proteins going about their business inside cells.

Protein tags spread throughout a cell after photoactivation (1 sec, 2 min, and 9 min)

The new tags could be used to locate specific proteins and track their movements and how they degrade. They could also help monitor the progression of diseases and the movement of cells in live animals.

"It is a visually powerful tool for looking at protein dynamics," says Jennifer Lippincott-Schwartz, who led the study at the National Institute of Child Health and Human Development at the NIH in Bethesda, Maryland.

In the movies, the researchers track fluorescent proteins rapidly disseminating from the nucleus into the cytoplasm of living cells. The nucleus burns bright green at first; then, as proteins spread to the outer reaches of the cell, the color diffuses.

Lippincott-Schwartz studies "traffic patterns" in cells to investigate fundamental questions about how cells work. She compares looking at proteins in cells to viewing cars from the window of an airplane: The vehicles appear too small to track, but it might be possible if they have color labels.

"We put a tag on some of the proteins and follow where they're moving," Lippincott-Schwartz says.

The scientists made the tag by changing the way a green fluorescent protein called GFP absorbs light. The new marker glows only when it has been photoactivated, but is then bright for days, the researchers write in Science.

Green fluorescent proteins have been used as markers for years, and the new version, like its predecessors, does not interfere with a cell's activity.

The tag has already proved useful by helping researchers investigate lysosomes—the garbage disposals of cells. They found that proteins move extensively from one lysosome to another, suggesting that communication pathways exist between the structures.

Since the study was published, Lippincott-Schwartz has received dozens of requests from researchers wanting to use the tag in a variety of projects, such as following the path of neurons in the brain. She and her colleague George Patterson at NIH plan to develop tags that would allow double labeling of proteins in different colors—red and green.

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Patterson, G.H. & J. Lippincott-Schwartz. A photoactivatable GFP for selective photolabeling of proteins and cells. Science 297, 1873-1877 (September 13, 2002).

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