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Discovery of dynamic sub-cellular processes could lead to medical applications

Virginia Tech

The photos were taken through the confocal microscope in the Fralin Biotechnology Center. Copyright 2001. Permission is granted only for use with information from the news release.

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BLACKSBURG, Va., Nov. 12, 2001 -- One of the key processing sites for proteins in cells is fundamentally more dynamic than scientists have traditionally believed, opening the possibility of harnessing cellular processes to benefit human health, according to Virginia Tech biochemist Brian Storrie.

Storrie and three other Virginia Tech researchers report in an article published today (November 12, 2001) in the Journal of Cell Biology that the proteins making up the Golgi apparatus in all cells are constantly being renewed. The research upon which the article is based was funded by the National Science Foundation.

"This is a central finding," Storrie said. "These recycled proteins are portals to the inside of the cell. These portals could be very useful."

Along with biochemists Suzanne Miles and Heather McManus and chemical engineer Kimberly E. Forsten, Storrie reported that the Golgi apparatus is not a fixed structure, but that every component of it is recycled through the endoplasmic reticulum. This recycling allows the replacement of frayed proteins, acting as a kind of quality control to ensure the structure can perform its function.

Potential practical applications of the finding include delivery of medicines to very specific locations in cells, and as a tool available to researchers to modify the cells to produce compounds for use in pharmaceuticals and for other uses. Reaching a practical use for the discovery is still a far step from this fundamental finding, Storrie said.

"But just eight years ago no one would have thought the Golgi apparatus is recycled and renewed," he noted.

The Golgi apparatus is a complex organelle. It is involved in the processing of proteins destined for either secretion or for the outer surface of the cell. Traditionally, scientists have looked on the Golgi apparatus as a fixed structure that processed proteins in an assembly-line fashion.

The organelle is a cup-shaped arrangement of layers of flattened sac-like membranes that's located in a characteristic place near the cell's nucleus. Proteins are processed through the layers of the Golgi apparatus, with enzymes in each layer causing modifications as the proteins proceed through the layers, finally to be shuttled into vesicles that take them to the cell's surface.

Vesicles are bubble-like containers that bud from the Golgi apparatus and transport proteins to the cell's surface membrane. The vesicles themselves are made of proteins, which are absorbed by the surface membrane when they have completed their mission.

Proteins are delivered to the Golgi apparatus for processing in vesicles that bud from the endoplasmic reticulum. Therefore, Storrie said, there is a constant flow of materials from the endoplasmic reticulum through the Golgi and to the cell's outer surface.

Storrie said Tommy Nilsson, a scientist with the European Molecular Biology Laboratory in Heidelberg, Germany, helped the Virginia Tech researchers develop a method to block the flow of proteins into the Golgi apparatus. As expected, that resulted in the depletion and eventual disappearance of the Golgi structure. Traditional wisdom held that the proteins making up the structure traveled to the cell's outer surface, where they were absorbed.

But by using sophisticated technology to mark the proteins in the Golgi apparatus, the scientists discovered that the proteins from the structure itself were dispersed to unexpected areas of the cell. The article says the finding "suggests that the entire Golgi apparatus continuously being assembled and disassembled...."

Storrie is now pursuing research in conjunction with the Carilion Biomedical Institute in Roanoke, Va., to see if compounds can be attached to the dispersing proteins for delivery to specific areas of the cell. If practicable, the procedure could be used to deliver precise amounts of medicines to precise locations.

In some applications, biotechnologists depend upon the secretion of compounds by cells to obtain materials for pharmaceuticals or for industrial applications. Storrie said this new understanding of the Golgi apparatus might in some cases allow scientists to develop cell secretions that more nearly fit their needs.

Storrie said he observed the first hint of this process in the mid-90s when he was helping a doctoral student put together a thesis problem. It was just in the last year, however, that the concept crystallized that the entire Golgi apparatus was constantly assembling, disassembly, and reassembling.

"I now know how to take it apart," Storrie said. "But I can't put it together. I would like very much to continue this research to learn how to put it together."



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