Cellular Transport and the Nobel Prize for Medicine

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The 2013 Nobel Prize in Physiology or Medicine was announced yesterday [1]. The prize was awarded to three U.S. scientists for their work on how the cell coordinates its transport system to shuttle proteins and other molecules from one location to another.

The prize of 8-million-Swedish-krona ($1.2-million USD) was divided evenly to Randy W. Schekman, age 65, at the University of California at Berkeley; James E. Rothman, age 63, at Yale University in New Haven, Connecticut; and Thomas C. Südhof, age 58, at Stanford University, for their discoveries of machinery regulating vesicle traffic, a major transport system in cells.

Why is cellular transport important?

A cell is a tiny factory that produces and exports molecules. Proper functioning of the cells in the body depends on getting the right molecules to the right place at the right time. The organization and transport of molecules is accomplished via small fat-encased bubbles called vesicles that shuttle cargo between organelles or fuse to other structures to release their cargo outside the cell. The vesicle transport system is critical for a variety of physiological processes, ranging from signaling in the brain to release of hormones and immune cytokines.

In the late 1970s, Randy Schekman was exploring the genetic mechanisms that control vesicle transport. Schekman identified three classes of genes that control different facets of the cell’s transport system.

In the 1980s and 1990s, James Rothman discovered that a protein complex enables vesicles to fuse with their target membranes (pictured in orange above). This lock and key mechanism ensures that the vesicle fuses at the right location and that cargo molecules are delivered to the correct destination.

Also in the 1990s, Thomas Südhof was studying how nerve cells communicate in the brain. Calcium ions were known to be involved in vesicle cargo release, and Südhof searched for calcium sensitive proteins in nerve cells. He identified the molecular machinery (pictured in purple above) that responds to an influx of calcium ions (Ca2+) and triggers vesicle fusion.

The Nobel Assembly at Karolinska Institutet in Sweden said in a statement [1]:

Through their discoveries, Rothman, Schekman and Südhof have revealed the exquisitely precise control system for the transport and delivery of cellular cargo. Disturbances in this system have deleterious effects and contribute to conditions such as neurological diseases, diabetes, and immunological disorders.

The work of Schekman, Rothman and Südhof on vesicle transport — recognized today as a fundamental process in cell physiology — may have far-reaching impact. Scientists have discovered vesicles outside cells. These extracellular vesicles are increasingly recognized for their participation in the pathogenesis of various diseases, including cancer, infectious diseases and neurodegenerative disorders, as well as atherosclerosis, thromboembolism, osteoarthritis, chronic renal disease and pulmonary hypertension, and periodontitis [2-3]. In addition, extracellular vesicles are likely to have therapeutic applications in large-molecule drug delivery [3].

References

1. The Nobel Prize in Physiology or Medicine 2013 – Press Release. Nobelprize.org. 7 Oct 2013.
2. Andaloussi et al. Extracellular vesicles: biology and emerging therapeutic opportunities. Nature Reviews Drug Discovery 2013 Vol: 12(5):347-357. DOI: 10.1038/nrd3978
   View abstract
3. Anderson et al. Role of extracellular membrane vesicles in the pathogenesis of various diseases, including cancer, renal diseases, atherosclerosis, and arthritis. Lab Invest. 2010 Nov;90(11):1549-57. DOI: 10.1038/labinvest.2010.152. Epub 2010 Aug 30.
   View abstract