Description du projet
Formation et remodelage des synapses neuronales
Les synapses neuronales jouent un rôle fondamental dans le traitement des informations et dans le stockage et la récupération des mémoires. Le compartiment présynaptique est responsable du stockage et de la libération des neurotransmetteurs, la composante postsynaptique recevant le signal du neurotransmetteur et le transformant en réponse cellulaire. Les scientifiques du projet SynapseBuild, financé par l’UE, s’intéressent aux vésicules synaptiques (VS) qui transportent les neurotransmetteurs. Ils étudieront notamment le mécanisme de formation et de transport des VS dans les neurones à l’aide de plusieurs technologies de pointe. Les résultats permettront de faire la lumière sur le remodelage dynamique du compartiment présynaptique, comblant ainsi une lacune essentielle dans les connaissances en neurosciences.
Objectif
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.
Champ scientifique
Programme(s)
Thème(s)
Régime de financement
ERC-ADG - Advanced GrantInstitution d’accueil
12489 Berlin
Allemagne