2016 Balzan Prize for Molecular and Cellular Neuroscience, including neurodegenerative and developmental aspects
For his pioneering studies on the molecular characterization of synaptic vesicles and the roles of protein complexes in the process of exocytosis – an essential mechanism for the transmission of signals in the nervous system.
Reinhard Jahn, born in Leverkusen, Germany, in 1950, earned his doctoral degree in Biology and Chemistry at Göttingen University. After a period in the US as a postdoctoral fellow at Yale University and as an assistant professor at Rockefeller University, he returned to Germany to direct a Young Investigator Group at the Max-Planck Institute for Psychiatry in Munich. He returned once more to the USA (as Professor and Associate Howard Hughes Investigator at Yale University) before settling in Göttingen, as Director of the Neurobiology Department at the Max-Planck Institute
for Biophysical Chemistry (since 1997).
Synaptic transmission is the major mechanism by which neurons in our brain communicate with each other. When a nerve impulse arrives at the nerve terminal, it causes the release of a signaling chemical – the neurotransmitter – by prompting the fusion of small vesicles with the plasma membrane (exocytosis). These synaptic vesicles contain the neurotransmitter, which is expelled into the narrow space between the sending and receiving neurons. This process may happen more than 100 times per second in a given nerve terminal, which requires an efficient and extremely fast mechanism of action.
The work of Reinhard Jahn and his collaborators has substantially improved our knowledge about the molecular details of this process. First, he made a major contribution to the identification of the synaptic vesicle protein synaptotagmin, the Ca++-sensor for triggering exocytosis. Since the 1950s it had been known that an influx of Ca++-ions into the nerve terminal triggers the process of neurotransmitter release. However, the molecule responsible was unknown until Jahn, together with Südhof, demonstrated the Ca-binding properties of synaptotagmin, making this protein the major candidate for the Ca++-sensor at the synapse. In the 1980s evidence had been provided that a complex of synaptic proteins (the so-called SNARE complex consisting of Synaptobrevin, Syntaxin, and SNAP-25) is involved in many forms of membrane fusion. The work of Reinhard Jahn and collaborators contributed the most decisive insights into the mechanisms of action of the complex. He identified the SNARE proteins as targets of clostridial neurotoxins (as did Cesare Montecucco, Padua) and as valuable tools for the study of neurotransmitter release. He then determined the topology of the SNARE complex, first by immunolabeling, and later, together with Brunger, by resolving its crystal structure. More recently, Reinhard Jahn’s proteomic study of the molecular constituents of synaptic vesicles has been very important, culminating in a three-dimensional molecular model of a synaptic vesicle. At least two of Reinhard Jahn’s discoveries – the topology and structure of the SNARE complex and the vesicular proteome – have transformed our understanding of presynaptic function, and are included in most neurobiology textbooks.