By Jess Devonport, Marketing and Communications Officer at the Society of Biology and one-time owner of a pair of shoes that are still lost in the post.
The Nobel Prize in Physiology or Medicine 2013 was awarded to James E Rothman, Randy W Schekman, and Thomas C Südhof for their discoveries of the “machinery regulating vesicle traffic, a major transport system in the cell”.
In the busy city of the cell, the “machinery regulating vesicle traffic” is the Royal Mail; and, like the Royal Mail, things can go wrong. The difference is that when Royal Mail deliveries go wrong, you have the minor inconvenience of going to the sorting office to collect your new shoes, but problems with the cellular postal service can lead to a whole host of nasty diseases including neurological and immunological disorders, and diabetes. Rothman, Schekman, and Südhof were interested in how this transport system is regulated and controlled.
A type of vesicle – a peroxisome in a human cell. Peroxisomes break down fatty acids in the cell.
In order to stop the contents of the cell becoming a soupy mess, molecules are packaged into vesicles, which prevents them causing damage or interacting with other molecules at the wrong time or place.
Schekman looked at the genetic controllers of the system; using yeast cells, he identified those with defective transport systems. In these cells, the vesicles would accumulate at certain points, like your motorcycle courier is caught in a traffic jam. By looking at where the blockages occurred, he was able to identify 23 gene mutations that caused the congestion, and the three classes of gene that controlled the traffic.
Rothman took this one step further, and looked at how the packages are delivered in mammalian cells. He identified several proteins that worked together to allow the vesicles to dock and fuse with the target membrane. These proteins only work in specific combinations, ensuring the contents is delivered to the right location, like a postcode.
Rothman and Schekman also noticed that the genes Schekman had identified in yeast coded for proteins that corresponded to the ones Rothman had been studying in mammals. This meant that these genes hadn’t changed much since the species evolved from their common ancestor.
Rothman and Schekman had discovered how the vesicles deliver their contents throughout the cell, but Südhof was interested in when this happens. Südhof looked at how nerve cells communicate with each other, through the release of chemical signals, or neurotransmitters. Vesicles containing neurotransmitter can only release their contents when the cell needs to signal to an adjacent cell. He wanted to know how the cell controlled the timing of the delivery so precisely. Calcium ions were already known to be involved in nerve cell signalling, so Südhof looked for calcium-sensitive proteins that were also needed for vesicle fusion with the cell membrane. He identified the protein machinery that responds to rising levels of calcium in the cell and binds to the outer cell membrane.
The combined discoveries of Rothman, Schekman, and Südhof have shown how this crucial cellular process works, and stops the cell from going postal.