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October 7, 2013
The 2013 Medicine/Physiology Nobel: Traffic
This year's Medicine Nobel is one that's been anticipated for some time. James Rothman of Yale, Randy W. Schekman of Berkeley, and Thomas C. Südhof of Stanford are cited for their fundamental discoveries in vesicular trafficking, and I can't imagine anyone complaining that it wasn't deserved. (The only controversy would be thanks, once again, to the "Rule of Three" in Alfred Nobel's will. Richard Scheller of Genentech has won prizes with Südhof and with Scheller for his work in the same field).
Here's the Nobel Foundation's scientific summary, and as usual, it's a good one. Vesicles are membrane-enclosed bubbles that bud off from cellular compartments and transport cargo to other parts of the cell (or outside it entirely), where they merge with another membrane and release their contents. There's a lot of cellular machinery involved on both the sending and receiving end, and that's what this year's winners worked out.
As it turns out, there are specific proteins (such as the SNAREs) imbedded in intracellular membranes that work as an addressing system: "tie up the membrane around this point and send the resulting globule on its way", or "stick here and start the membrane fusion process". This sort of thing is going on constantly inside the cell, and the up-to-the-surface-and-out variation is particularly noticeably in neurons, since they're constantly secreting neurotransmitters into the synapse. That latter process turned out to be very closely tied to signals like local calcium levels, which gives it the ability to be turned on and off quickly.
As the Nobel summary shows, a lot of solid cell biology had to be done to unravel all this. Scheckman looked for yeast cells that showed obvious mutations in their vesicle transport and tracked down what proteins had been altered. Rothman started off with a viral infection system that produced a lot of an easily-trackable protein, and once he'd identified others that helped to move it around, he used these as affinity reagents to find what bound to them in turn. This work dovetailed very neatly with the proteins that Scheckman's lab had identified, and suggested (as you'd figure) that this machinery was conserved across many living systems. Südhof then extended this work into the neurotransmitter area, discovering the proteins involved in the timing signals that are so critical in those cells, and demonstrating their function by generating mouse knockout models along the way.
The importance of all these processes to living systems can't be overstated. Eukaryotic cells have to be compartmentalized to function; there's too much going on for everything to be in the same stew pot all at the same time. So a system for "mailing" materials between those regions is vital. And in the same way, cells have to communicate with others, releasing packets of signaling molecules under very tight supervision, and that's done through many of the same mechanisms. You can trace the history of our understanding of these things through years of Nobel awards, and there will surely be more.
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