Scientists believe the research could eventually lead to new medicines for epilepsy, diabetes and other metabolism deficiencies.
The work has already helped doctors diagnose a severe form of epilepsy and immune deficiency diseases in children. And it has helped guide research into the brain and many neurological diseases, and opened the door for biotech companies to make yeast pump out large quantities of useful proteins like insulin.
The $1.2 million prize will be shared by James Rothman, 62, of Yale University, Randy Schekman, 64, of the University of California, Berkeley, and Dr. Thomas Sudhof, 57, of Stanford University.
They unlocked the mysteries of the cell's internal transport system, which relies on bubble-like structures called vesicles to deliver substances the cell needs. The fleet of vesicles is sort of the FedEx of the cellular world.
When a pancreas cell releases insulin or one brain cell sends out a chemical messenger to talk to a neighboring one, for example, the vesicles have to deliver those substances to the right places on the cell surface. They also ferry cargo between different parts of a cell.
"Imagine hundreds of thousands of people who are traveling around hundreds of miles of streets; how are they going to find the right way? Where will the bus stop and open its doors so that people can get out?" Nobel committee secretary Goran Hansson said. "There are similar problems in the cell."
Jeremy Berg, former director of the National Institute of General Medical Sciences in Bethesda, Md., said the prize was long overdue and widely expected because the work was "so fundamental and has driven so much other research."Berg, who now directs the Institute for Personalized Medicine at the University of Pittsburgh, said the work provided the intellectual framework that scientists use to study how brain cells communicate and how other cells release hormones.
So the work has indirectly affected research into virtually all neurological disease as well as other diseases, he said.
In the 1970s, Schekman discovered a set of genes that were required for vesicle transport. Rothman revealed in the 1980s and '90s how vesicles delivered their cargo to the right places. Also in the '90s, Sudhof identified the machinery that controls when vesicles release chemical messengers from one brain cell that let it communicate with another.
"This is not an overnight thing. Most of it has been accomplished and developed over many years, if not decades," Rothman said.
Rothman said he lost grant money for the work recognized by the Nobel committee, but he will now reapply, hoping the prize will make a difference in receiving funding.
Schekman said he was awakened at 1 a.m. at his home in California by the chairman of the prize committee, just as he was suffering from jetlag after returning from a trip to Germany the night before.
"I wasn't thinking too straight. I didn't have anything elegant to say," he told The Associated Press. "All I could say was 'Oh, my God,' and that was that."
He called the prize a wonderful acknowledgment of the work he and his students had done. "I called my lab manager and I told him to go buy a couple bottles of Champagne and expect to have a celebration with my lab," he said.
Sudhof, who was born in Germany but moved to the U.S. in 1983 and also has American citizenship, told the AP he received the call from the committee while driving in Spain, where he was due to give a talk.
"And like a good citizen I pulled over and picked up the phone," he said. "To be honest, I thought at first it was a joke. I have a lot of friends who might play these kinds of tricks."
The medicine prize kicked off this year's Nobel announcements. The awards in physics, chemistry, literature, peace and economics will be announced this week and next. Each prize is worth 8 million Swedish kronor ($1.2 million).
Rothman and Schekman won the Albert Lasker Basic Medical Research Award for their research in 2002 - an award often seen as a precursor of a Nobel Prize. Sudhof won a Lasker last month.
Established by Swedish industrialist Alfred Nobel, the Nobel Prizes have been handed out since 1901.
Last year's Nobel in medicine went to Britain's John Gurdon and Japan's Shinya Yamanaka for their contributions to stem cell science.
Karl Ritter reported from Stockholm. Associated Press writers Malin Rising in Stockholm, Frank Jordans in Berlin, Matt Surman in London, and Stephen Singer in Hartford, Conn. contributed to this report.