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Nobel prize is awarded for studies of intracellular transport mechanisms

BMJ 2013; 347 doi: https://doi.org/10.1136/bmj.f6087 (Published 08 October 2013) Cite this as: BMJ 2013;347:f6087
  1. Geoff Watts
  1. 1London

The 2013 Nobel prize for medicine or physiology has been awarded to one German and two US cell biologists for their exploration of the mechanisms by which hormones, neurotransmitters, and other such materials are transported in tiny vesicles through the cell to their point of delivery.

The three winners are Randy W Schekman, born in 1948 and based in the University of California at Berkeley, James E Rothman, born in 1950 and working at Yale University, and Thomas C Südhof, born in 1955 in Göttingen, Germany, and now at Stanford University.

Daniel Davis, professor of immunology at Manchester University’s Collaborative Centre for Inflammation Research and author of a new book, The Compatibility Gene, is not surprised by the choice of winners. “They’ve been in the frame for some while,” he says. But he added that the Nobel judges’ decision was a timely and forward looking one.

“The prize has moved from rewarding the identification of individual genes and proteins. Now it’s about the dynamics of how things play out in space and time—how vesicles traffic their cargo around different parts of the cell. It’s a major frontier of research.”

The cell’s internal transport system plays an indispensible role in its smooth operation. Enzymes, cytokines, and other such molecules have to be moved at exactly the right time from their site of production within the cell to the location at which they’re needed or from which they’ll be exported.

The bubble-like vesicles in which they are carried through the cell are surrounded by membranes. When the cargo is for export—as with a neurotransmitter in a nerve, for example—these membranes fuse with those surrounding the whole cell, so releasing the contents to the exterior.

Schekman’s contribution to the study of the transport system grew out of his interest in the genetic basis of its control. Using yeast as a model, he identified cells with mutated genes in which the system failed. He went on to identify three classes of gene, each controlling a different aspect of the transport mechanism.

Rothman’s concern was with the means by which vesicles attach to and fuse with their target membranes. He discovered that proteins on their respective surfaces bind to each other like the two halves of a zipper. This binding occurs only between specific combinations of protein, which is how the vesicle’s cargo is delivered to the correct location.

Südhof’s work has shown how neurotransmitters are released from nerve cells. In the 1990s he identified calcium sensitive proteins in nerve cells that respond to an influx of calcium ions and cause the vesicles to fuse with the cell’s outer membrane, so releasing their chemical cargo at the appropriate moment.

As the members of the Nobel prize committee pointed out, “Defective vesicle transport occurs in a variety of diseases, including a number of neurological and immunological disorders, as well as in diabetes.”

However, the immediate medical implications of the work may be limited. “Creating drugs that directly target the movement of things through cells is a huge area, but it has a long way still to go,” said Davis. “There’s still a lot to understand. I think we’re some way from realizing the full potential of this area of science in the medical setting.”

Notes

Cite this as: BMJ 2013;347:f6087

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