Yeast provides evidence for continuous membrane theory

April 5, 1999

Researchers at the University of Chicago have new evidence to support a controversial theory about tiny intracellular structures called organelles. Their findings support the theory that certain organelles form an interconnected system where one organelle gives rise to another through outgrowths of its own membrane.

Their discoveries will also shed light on disorders such as Menkes disease and polycystic kidney disease, which are caused by defects in Golgi function.

The researchers studied a particular region of the cell where an organelle called the endoplasmic reticulum (ER) seems to give rise to another organelle called the Golgi apparatus. This process occurs at specific places along the ER called transitional ER (tER) sites.

"Our work strongly suggests that the Golgi apparatus grows directly out of the tER," says Benjamin Glick, assistant professor at the University of Chicago and lead author of the paper in the April 5, 1999 issue of the Journal of Cell Biology.

The Golgi apparatus, which consists of a stack of pancake-shaped membranes called cisternae, is responsible for modifying and packaging proteins for export to the cell surface. According to the membrane outgrowth theory, Golgi cisternae are transient structures, with new cisternae constantly being generated at tER sites.

Glick realized he had a unique opportunity to test this hypothesis when he noticed very different-looking Golgi formations in two yeast species: Pichia pastoris, which has the typical coherent stacked Golgi cisternae, and Saccharomyces cerevisiae, or brewer's yeast, which has dispersed individual cisternae scattered throughout the cell.

"We used these two yeasts because they are closely related, yet they have completely different Golgi structures. Saccharomyces is definitely an oddity because almost every other kind of cell has well-organized Golgi stacks. We reasoned that the dispersed Golgi in Saccharomyces might be explained by an unusual organization of the tER," Glick says.

Glick and his team created a fluorescent protein that specifically marks tER sites and introduced it into Pichia and Saccharomyces cells. The result was striking. A single Pichia cell has a small number of tER sites, each giving rise to a Golgi stack; but in Saccharomyces, the entire ER lights up with the striking. A single Pichia cell has a small number of tER sites, each giving rise to a Golgi stack. But in Saccharomyces, the entire ER lights up with the fluorescent marker, indicating that Saccharomyces lacks well-defined tER sites, and that Golgi cisternae can therefore arise from any place along the ER.

Glick is not sure why Saccharomyces has a delocalized tER and a dispersed Golgi. "This strange organization might somehow be beneficial for this yeast. Or it might just be an accident of evolution. At this stage we're still guessing," he says. "But we can take advantage of the differences between the two yeasts to uncover the mechanisms that produce tER sites."

Like Pichia, mammalian cells have discrete tER sites that give rise to Golgi cisternae. By using yeasts as a model system, the researchers hope to arrive at a broad understanding of how Golgi stacks are formed and maintained.

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