In graduate school, while you are building your super-specialized knowledge base there are often particular labs whose work you are on the look-out for while searching for new papers to read. Sometimes it’s a competitor that you’re keeping tabs on, other times it’s your science crush, and more often it’s just scientists whose work is consistently thorough and enlightening. For me, studying synaptic development, one of those labs was the Sudhof lab at Stanford. When I heard he had won the Nobel prize a few weeks ago I was pretty excited to actually know what work contributed to that prize without reading the press release. Cell press has made the journal article detailing his seminal discoveries available to everyone. The award was made to those contributing to discovery of the machinery regulating vesicle traffic, the major transport mechanism within a cell. Dr. Sudhof’s contributions were specific to vesicle trafficking within nerve cells.
Sudhof’s seminal work focused on multiple forms of a protein called synaptotagmin. This protein is attached to synaptic vesicles which are packages of neurotransmitters that are released from a cell when that cell is activated. Neurotransmitters are chemical messengers that then travel to the next cell and carry the signal of activation. Sudhof showed that different types of synaptotagmin are expressed all throughout the brain. He also showed that they are at areas called the synapse, the connection between two cells. One of the components of his work most critical to the future of neuroscience was his discovery that 3 of the 4 types of synaptotagmin bind to calcium.
When a nerve cell is activated, it is flooded with calcium near the synapse or connection to another cell. This activations leads to the release of neurotransmitters from the receiving cell. This discovery of the calcium binding ability of synaptotagmin began to unravel the details of this process. When calcium comes in, it binds to the synaptotagmin that is attached to the vesicles loaded with neurotransmitter. This changes the synaptotagmin slightly and helps it to work with the other machinery in the cell to allow that vesicle to dump it’s neurotransmitter contents outside the cell. Synaptotagmin is the link connecting calcium to neurotransmitter release.
Synaptotagmin also can bind to a protein called AP-2. This suggests that in addition to helping vesicles dump their neurotransmitters outside the cell, synaptotagmin can also help make new vesicles by attaching to the membrane and pulling it in to make a new vesicle (endocytosis). These basic characterizations of the synaptotagmin protein were critical to the understanding of the basic function of nerve cells. The connection of calcium to vesicle fusion is truly one of the major discoveries in neuroscience. While Sudhof’s work is couched in the study of vesicle trafficking in general, this work has been incredibly influential in neuroscience.
Congratulations Thomas Sudhof!