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Mechanisms of Presynaptic Biogenesis and Dynamic Remodeling

Descrizione del progetto

Formazione e rimodellazione delle sinapsi neuronali

Le sinapsi neuronali svolgono un ruolo strumentale nell’elaborazione delle informazioni e nell’immagazzinamento e nel recupero dei ricordi. Il compartimento presinaptico è responsabile dell’immagazzinamento e del rilascio di neurotrasmettitori, mentre la parte postsinaptica riceve il segnale del neurotrasmettitore e lo trasforma in una risposta cellulare. Gli scienziati del progetto SynapseBuild, finanziato dall’UE, sono interessati alle vescicole sinaptiche (VS), che trasportano i neurotrasmettitori. In particolare, studieranno il meccanismo di formazione e trasporto nei neuroni delle VS utilizzando una serie di tecnologie all’avanguardia. I risultati faranno luce sulla dinamica che rimodella il compartimento presinaptico, colmando una lacuna di conoscenze cruciale nelle neuroscienze.

Obiettivo

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.

Meccanismo di finanziamento

ERC-ADG - Advanced Grant

Istituzione ospitante

FORSCHUNGSVERBUND BERLIN EV
Contribution nette de l'UE
€ 2 496 875,00
Indirizzo
RUDOWER CHAUSSEE 17
12489 Berlin
Germania

Mostra sulla mappa

Regione
Berlin Berlin Berlin
Tipo di attività
Research Organisations
Collegamenti
Costo totale
€ 2 496 875,00

Beneficiari (1)