The cellular post office

Earlier this month, the Nobel Assembly at the Karolinska Institutet announced the winners of the 2013 Nobel Prizes. The prize in Physiology or Medicine was awarded jointly to James Rothman, a Yale professor of cell biology, Randy Schekman, a biologist at UC Berkeley, and Thomas Sdhof, a professor of molecular and cellular physiology. Their work focuses on the mechanisms by which molecules are transported within or between cells.

“These beautiful discoveries have importance for the understanding of the human body and obviously implications for diseases in various organs such as the nervous system, diabetes and immune disorders,” said Jan-Inge Henter, a scientist at the Karolinska Institutet.

The transportation of molecules-such as neurotransmitters or hormones-in cells is incredibly important. Generally, this molecular “cargo” is packaged in vesicles-small compartmentalized sacs-to be transported to another cell or another location in the same cell.

When proteins are synthesized, they need to be transported within a cell. Not all of these proteins are meant to be localized in the same area. Imagine a simple example of a cell. Our hypothetical cell synthesizes two kinds of proteins: protein A and protein B. These two proteins need to be segregated to opposite sides of the cell. In order for this to happen, there has to be a way of recognizing proteins A and B, as well as sorting them into different compartments.

The work of earlier scientists, including several previous Nobel laureates, clarified how this system works. It was already known that vesicles played a critical role in the transportation of molecular cargo by containing the molecules and keeping them separated from the external environment to ensure their safety. But until recently, one question remained: How are molecules sent to the right destination with precision?

Schekman’s research compared normal yeast cells with mutated ones to identify the genes that control vesicle transportation. Rothman identified the proteins that allow vesicles to fuse with their target membranes-like a small soap bubble being absorbed by a larger one. Sdhof discovered the mechanism that detects calcium ions and causes vesicle fusion, which explains how signals can be transmitted from one nerve cell to another with temporal precision.

These findings have changed the way we view the transportation of molecular cargo. This is important because molecular signals are continuously released within a cell to synchronize the cell’s activities, and outside of the cell to communicate with other nearby cells, or to the bloodstream to reach distant targets.

Disturbances at any step in this process can contribute to neurological diseases, diabetes, or immunological disorders.