Project description
Formation and remodelling of neuronal synapses
Neuronal synapses play an instrumental role in the processing of information and in storing and retrieving memories. The presynaptic compartment is responsible for storing and releasing neurotransmitters, while the postsynaptic part receives the neurotransmitter signal and transforms it into a cellular response. Scientists of the EU-funded SynapseBuild project are interested in synaptic vesicles (SV), which carry neurotransmitters. In particular, they will investigate the mechanism of SV formation and transport in neurons using a number of cutting-edge technologies. Results will shed light on the dynamic remodelling of the presynaptic compartment, filling a crucial knowledge gap in neuroscience.
Objective
Our ability to move, to process sensory information or to form, store and retrieve memories crucially depends on the function of neuronal synapses. Synapses comprise a presynaptic compartment harboring the machinery for neurotransmitter release and an associated postsynaptic compartment that processes the neurotransmitter signal. During decades of research we have acquired a wealth of knowledge regarding the mechanisms of neurotransmitter release and information processing in the postsynaptic compartment. In great contrast, we know surprisingly little about the pathways that direct the formation, transport, and assembly of the complex molecular machines that make up a functional presynapse. In particular, it is unclear where and how synaptic vesicle (SV) precursors are formed in the neuronal cell body, in which form they are transported along the axon, and which maturation steps occur to allow their assembly into functional units for neurotransmitter release. How cytoplasmically synthesized presynaptic active zone (AZ) proteins that organize SV release sites are transported and assembled is equally unclear. Here, we combine genome engineering in stem cell-derived neurons and genetically altered mice with proteomic, high-resolution imaging and systems biology approaches to identify the origin and composition of SV and AZ precursors, dissect the mechanisms of their axonal transport and integration into developing synapses and unravel the pathway that controls axonal transport and presynaptic assembly of newly made SV and AZ proteins to set synaptic weight. Our high risk/ high gain studies will yield groundbreaking insights into the mechanisms that mediate the formation, maintenance, and dynamic remodeling of the presynaptic compartment during development and thereby fill a crucial knowledge gap in neuroscience. Furthermore, they may pave the way for the future development of therapeutics to cure nerve injury or neurological disorders linked to synapse dysfunction.
Fields of science
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Funding Scheme
ERC-ADG - Advanced GrantHost institution
12489 Berlin
Germany