Molecular Nanomachines of the Presynaptic Terminal

Synaptic transmission is the basis of neuronal communication, and is thus the most important element in brain functions ranging from sensory input to information processing. Changes in synaptic transmission can result in the formation or dissolution of memories, and can equally lead to neurological and psychiatric disorders. The proteins composing the synapse, and their respective functions, are getting increasingly known. One aspect that has become evident in the last years is that most synaptic functions are performed not by single proteins, but by highly organized multi-protein machineries, which interact dynamically in order to provide responses optimally suited to the needs of the neuronal network. In order to decipher synaptic and neuronal function, it is essential to understand the organisational, morphological and functional aspects of these machineries, of the molecular nanomachines that form the synapse. Therefore, after consolidated knowledge in single proteins and single steps in synaptic functions,the field of synaptic transmission is now swerving to more wide-ranging studies, which encompass the entire makeup of the synapse, or of some of its machineries. We feel that reviews on synaptic transmission should not lag behind this trend in synaptic science. Therefore, we propose a research topic based on the molecular nanomachines of the synapse. We propose to assemble a strong team that will describe the different machines of the presynaptic bouton, in all of their aspects. The following machines will be tackled:
- The active zone, where the vesicles fuse, with specific reviews dealing on its morphology, on its protein composition, and on its dynamics, both in general and in specialized synapses.
- The peri-active zone, where the vesicle endocytosis takes place.
- The neurotransmitter release machinery.
- The vesicle recycling clathrin-connected machinery.
- The adhesion complexes.
- The synaptic cytoskeleton.
- The core of the synaptic vesicle cluster.
- The synaptic vesicle itself.

We feel that this focused topic will go along with the current wave of proteomic and functional research in the synapse, and will therefore help in fine-tuning questions on the many unknown issues in the synapse, as well as instructing the younger generations of neuronal researchers.