High tech movies reveal information transfer within cells

Like houses are divided into rooms, cells are divided into compartments, each with their own functions and bounded by their own membrane walls. These cell compartments float about the cell like bubbles, bumping and fusing together when the occupants of two rooms need to come together.

Now, Dartmouth Medical School biochemists have devised a high tech way to watch, in living color, how these bubbles fuse, and what they have seen upends prior assumptions about the ways cell components transfer chemical information.

Their findings, published in the February 8 issue of the journal Cell, reveal a new mechanism of membrane fusion, a process that is essential for such life functions as nerve impulse transmission or hormone secretion in humans. This new research offers a practical method to study and, eventually, to modulate these fusion events, report the authors, William Wickner, MD, professor of biochemistry; graduate students Li Wang and E. Scott Seeley, and postdoctoral fellow Alexey Merz.

Most cell compartments are far too small to see under even a powerful light microscope. But the vacuole of baker's yeast, a widely-studied organism, has a membrane large enough to observe the structural details of each step in the fusion process.

Fusion between membranes requires an ordered cascade of protein activities that define each stage of the process. Employing advanced genetic techniques, the investigators tagged the membrane proteins that catalyze fusion with a green fluorescent protein label. This allowed them to track the proteins and visualize how two vacuoles in yeast fuse. They used time-lapse fluorescence microscopy, with a special microscope DMS obtained through a gift from the Rippel Foundation, to generate computerized images that were strung together to provide a movie of fusion.

"We see that yeast vacuoles fuse by an entirely different mechanism than what had been postulated," said Wickner. "There does not appea

Contact: Steve Snyder
Dartmouth Medical School

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