Yale Scientists Give The Golgi Apparatus Its Own Identity, Paving The Way For More Targeted Cancer Research

Published in a recent issue of Nature, the discovery gives researchers a better understanding of the cell division process and of the processes present in the uncontrolled cell division that marks cancer.

In normal cell division, a mother cell divides into two daughters and the division is regulated until it stops. In a skin melanoma, for example, the cell division inexplicably starts up again and continues unregulated. This study could help cancer researchers understand why the regulation stops.

"Researchers once thought that the Golgi apparatus was no more than an outgrowth of an organelle called the endoplasmic reticulum," said Graham Warren, professor of cell biology at Yale and a leading expert in the field. "We’ve shown that it is an organelle within a cell that has its own autonomy and so must grow and divide to keep pace with the growth and division of the cell it inhabits."

The Golgi apparatus sorts and modifies cell products such as hormones, growth factors and digestive enzymes, and sends them to their final destinations within the cell. For example, the Golgi decides whether a given protein will leave the cell or be delivered to the cell surface or another destination. As with all other cellular organelles, the Golgi has to grow and divide and has to be inherited.

The Golgi apparatus is normally thought of as a stack of membrane compartments through which the secretory proteins pass, but Warren and colleagues have been able to show that the Golgi has an existence even when these membranes are removed from the apparatus.

"We found that there are proteins, which we term matrix proteins, that form a scaffold to organize the membranes," said Warren. "We think this scaffold might be the Golgi apparatus proper, responsible for its growth, division and partitioning between the two daughter cells."

In past research, Warren and his team have shown that the regrowth of a mother Golgi in the newly formed daughter cells requires a number of matrix proteins that are involved in putting the new Golgi complex together.

The significance of this new finding, Warren said, is at the basic cell biological level. "People have tended to think of organelles such as the Golgi in terms of the membranes, in part because this is the structure you see by electron microscopy," said Warren. "You don't see the matrix proteins. What we have done is to focus attention on these underlying structures, which might actually be more relevant to people interested in studying the biogenesis of these organelles."

Warren said his research brings together a broad spectrum of scientific disciplines, including traditional cell biology, biochemistry, molecular biology and structural biology.

"Now that we know that the Golgi is an independent organelle that has its own identity, we can start looking at it from a basic cell biology perspective that has medical implications for diseases like cancer, " said Warren.

Warren’s research team included Joachim Seemann and Marc Pypaert at Yale and Eija Jokitalo from the Institute of Biotechnology in Helsinki, Finland.