Three U.S.-based investigators who discovered how key molecules are transported within and outside the cell through vesicles were named co-winners of the 2013 Nobel Prize in Physiology or Medicine this morning.
James E. Rothman, Ph.D., of Yale University, Randy W. Schekman, Ph.D., of the University of California, Berkeley, and Thomas C. Südhof, M.D., of Stanford University were cited for their discoveries of molecular principles governing the system of vesicular transport within cells—through which, for example, insulin is released into the blood following its manufacture, while neurotransmitters are sent from one nerve cell to another.
The discoveries were likened to insights on how cargo is delivered to the right place at the right time within a large transportation system—in this case, the cell. Disorders associated with the transportation system are factors in conditions such as diabetes, immunological disorders, and neurological diseases.
“These beautiful discoveries have importance for our understanding of the human body and, obviously, implications for diseases in various organs,” Jan-Inge Henter, M.D., Ph.D., professor of clinical child oncology at the Karolinska Institute, told reporters during a press conference after the announcement.
He said the Nobel winners’ discoveries on the vesicle transportation system has enhanced researchers’ understanding of tetanus and may improved the treatment of inflammation in children by suggesting new diagnostics. As for diabetes, “we know that insulin is released by these vesicles, and we know that the immune system is regulated also by this vesicle transport mechanism.”
Dr. Schekman, professor of molecular and cell biology at UC Berkeley, used yeast as a model for studying the cell transportation system in the 1970s. Through a genetic screen, he identified yeast cells with defective transport machinery, giving rise to the equivalent of traffic congestion in a public transport system—namely the piling up of vesicles in parts of the cell. Dr. Schekman, who is also a Howard Hughes Medical Institute investigator, found that the cause of the congestion was mutated genes, which he identifed. He also identified three classes of genes that control different facets of the cell's transport system, providing new insights into the regulation of vesicle transport in the cell.
Some of the genes Dr. Schekman discovered in yeast, when coded, revealed proteins corresponding to those identified in mammals by Dr. Rothman, suggesting an ancient evolutionary origin of the transport system. Drs. Schekman and Rothman later joined to map critical components of the cell´s transport machinery.
By studying mammalian cells in the 1980s and 1990s, Dr. Rothman discovered that proteins on the vesicles enabled them to dock with their target membranes, then fuse by binding to each other as two sides of a zipper. Vesicles, he discovered, contain numerous proteins that bind only in specific combinations, ensuring that cellular “cargo” is delivered to a precise location.
The same principle operates inside the cell, when a vesicle binds to the cell´s outer membrane to release its contents, concluded Dr. Rothman, who is executive director of the Yale Center for High Throughput Cell Biology. At Yale he also holds the titles of Wallace Professor of Biomedical Sciences, professor of chemistry, and professor and chairman of cell biology.
Dr. Südhof discovered details of the mechanism by which nerve-cell signals touch off vesicular release of their contents: Neurotransmitters are released from vesicles that fuse with the outer membrane of nerve cells, using the machinery discovered by Drs. Rothman and Schekman. Because calcium ions were known to be involved in the process, Dr. Südhof searched in the 1990s for calcium-sensitive proteins in nerve cells. He identified molecular machinery that responds to an influx of calcium ions by directing neighbor proteins to rapidly bind vesicles to the outer membrane of the nerve cell.
The Nobel Prize in Physiology or Medicine was announced in a ceremony at Sweden’s Karolinska Institute. Each Nobel Prize includes 8 million Swedish kronor ($1.2 million).
“My first reaction was, 'Oh, my god!'” Dr. Schekman, 64, recalled after being awakened at his El Cerrito home with the good news at 1:30 a.m., according to a UC Berkeley announcement. “That was also my second reaction.”