October 7, 2013 | 3
This year’s Nobel Prize in medicine or physiology was—true to the often-overlooked second half of its name—awarded for discoveries in basic physiology. The 2013 prize recognizes ground-breaking research into how cells use simple bubbles of fatty molecules (known as vesicles [pdf]) to safely transport proteins and hormones from one compartment to another within cells as well as how those fatty bubbles enter and leave the cells. Three investigators will share in the 8 million Swedish Kroner ($1.25 million) prize: James E. Rothman of Yale University, Randy W. Schekman of the University of California at Berkeley, and Thomas C. Südhof at the Stanford University school of medicine.
This vesicle-transport system lies at the heart of nerve cells’ ability to communicate with each other by releasing neurotransmitters like serotonin and dopamine as well as the body’s ability to regulate its blood sugar levels using the insulin hormone. Toxins like botulin and tetanus are deadly precisely because they destroy the vesicle-transporting machinery.
Lots of textbook diagrams over the years have given the impression that cells are like water-filled balloons in which various parts—such as the information-packed nucleus and energy-producing mitochondria—just float around. In fact, the cells are highly compartmentalized—which allows the molecular pathways within the cell to occur more efficiently and in a very well-orchestrated manner. The whole process of moving the raw material—in the form of proteins or hormones—from one part of the cell to another takes place in transport bubbles. More specifically, these vesicles consist of a membrane of fatty molecules, which surrounds the proteins or hormone molecules and keeps them from being released at the wrong time or place.
While the vesicles themselves have long been known, figuring out how the transport system worked was no easy task. Starting in the 1970s, Randy Schekman studied yeast cells and found he could create mutant cells in which the vesicles simply piled up in the cell—going nowhere. He then identified the genes responsible for making sure the vesicles formed and got to where they needed to go.
But that doesn’t explain how these fatty bubbles release their cargo into another compartment. James Rothman started working on that problem in the 1980s. At the time, many researchers thought that the cells needed to be intact in order to study this process, but Rothman actually broke up the cells into fragments and showed that the fusing of a vesicle with the membrane of another cellular compartment could happen even on these fragments. Eventually he isolated proteins found on the outside of the vesicles that attached to other membranes and then opened up the vesicle like a zipper, releasing the contents.
Intriguingly, vesicles don’t just open up the second they have latched on to the surface of their cellular destination. It was up to Thomas Südhof to find and characterize a calcium-containing sensor that tells the vesicle when to release its cargo.
Oh and by the way, James Rothman wrote about this research for Scientific American back in 1996.
From the Scientific American digital site:
>> Budding Vesicles in Living Cells, by James E. Rothman and Leslie Orci, March 1996
If you have an institutional access to our deep archive, you can find two other articles by Rothman:
>>The Compartmental Organization of the Golgi Apparatus by James E. Rothman, Septembe r1985
>>The Assembly of Cell Membranes by Harvey F. Lodish, James E. Rothman, January 1979