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Molecular structure of the brain’s transport vessels revealed
Synapses are of enormous importance for the complex functioning of our brains – billions of nerve cells communicate never endingly over these tiny corridors. The language used in this process is made up of messenger materials, stored in miniscule membrane vesicles. Up to now, the molecular structure of these transporting vessels has been something of a mystery, being so small that conventional microscopes are not powerful enough observe them. Leibniz prizewinner Reinhard Jahn from the Max-Planck Institute for Biophysical Chemistry in Göttingen, Germany, has been dedicated to shedding some light on these issues and, together with an team of 22 international scientists, he has now succeeded in depicting these complex molecules in a representational model – a result of years of work. As the researchers have reported in Cell magazine (vol. 127, p. 831-846), it is now possible to paint a much more complete picture of these synaptic vessels, and many previous assumptions must be reconsidered.
Our brain consists of many billions of nerve cells, all connected in a complex network and constantly sending messages back and forth. The most important components of this communication are the synapses, through which nerve impulses are carried from one cell to the next. Whereas within the cell, signals are passed on electrically, the signal transmission in the synapses makes use of chemical messenger materials, called neurotransmitters. These are stored by the cell in small membrane vesicles, which serve as a storage medium. During signal transmission, the synaptic vesicles merge with the cell wall, open up and empty out their contents.
Laborious work to construct the first complex model
Fusion procedures such as these play a substantial role in each cell and are therefore of fundamental importance and interest to cell biologists. However, in the past, the limited figurative representations available posed a major obstacle to a deeper understanding of these processes- the structures involved are far too small to be visible with a conventional optical microscope. For some years, Reinhard Jahn, Director of the Department of Neurobiology at the Max-Planck Institute for Biophysical Chemistry in Göttingen, Germany, has been working on these problems and, piece by piece, has attempted to get to grips with unanswered questions - the synapses’ vesicles as being just one example. During his time in this field, Jahn has made many significant contributions to the overall understanding of cell-to-cell signal transmission. Among other achievements, Jahn identified several proteins that are vital to the process (Nature, vol. 395, 24. 9. 1998, and other publications), also examining the interactions between the various proteins in every detail. Now, the cell biologist, who was awarded the Leibniz Prize from the German Research Foundation (DFG) at the turn of the millennium, has again taken another important step forwards. Together with his 22 colleagues from around the world, he has constructed a representation of the synaptic vesicles in a complex atomic model. To do this, the researchers analyzed and quantitatively evaluated a broad range of data relating to the density, mass and quantity of the major molecules involved in the process. As the scientists reported in Cell magazine (Vol. 127, p.831-846), their work has resulted in the first molecular model of a cellular structure.
More proteins swimming on the surface than previously thought
This new spatial representation of the vesicles has brought to light the fact that previous assumptions regarding the structure of the vesicles must now be substantially rethought. "Before, the membranes were represented as smooth double layers of lipids, in which proteins swam around, much like icebergs in the sea", says Jahn, "Whereas actually, the surface is almost completely covered with proteins." Apart from the surprising density, the researchers were also surprised to discover that the membrane shell is utterly riddled with a variety of protein complexes. As well as well-known proteins, a number of completely unknown proteins have emerged in this discovery, which will be more closely examined in the years to come.
To help in this task is a completely new microscope technology, in which another colleague from the MPI for Biophysical Chemistry - Stefan Hell, Director of the Department of NanoBiophotonics - had a considerable hand in developing. In previous years, Hell has managed to improve existing optical microscopic procedures in such a way as to allow close the observation of molecular procedures, previously considered impossible. For his work, Hell has been awarded this year's German Future Prize, which was presented by German Federal President Horst Köhler at a ceremony on 23 November.
