TRANSSYNAPTICARCH
Molecular architecture of a prototypical trans-synaptic complex: GluD2-Cerebellin1-Neurexin1β
| Coordinatore | THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Organization address
address: University Offices, Wellington Square contact info |
| Nazionalità Coordinatore | United Kingdom [UK] |
| Totale costo | 221˙606 € |
| EC contributo | 221˙606 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | FP7-PEOPLE-2012-IEF |
| Funding Scheme | MC-IEF |
| Anno di inizio | 2014 |
| Periodo (anno-mese-giorno) | 2014-04-01 - 2016-03-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Organization address
address: University Offices, Wellington Square contact info |
UK (OXFORD) | coordinator | 221˙606.40 |
Mappa
Word cloud
Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.
Obiettivo del progetto (Objective)
'Chemical synapses in the central nervous system (CNS) employ a multitude of neuronal cell-surface receptors, adhesion proteins, secreted effector molecules, and proteoglycans. Within such vast network of interactions, synapse-spanning protein complexes mediate cell-cell adhesion, align pre- and postsynaptic specializations and exert bidirectional signaling, inducing pre- and postsynaptic differentiation. This proposal focuses on the “Glutamate receptor D2–Cerebellin1–Neurexin1β” trans-synaptic complex, a key component of the excitatory parallel fiber - Purkinje cell (PF-PC) synapse in the cerebellum. This tripartite interaction is essential for bidirectional synaptogenesis, and its specific disruption leads to impairment of cognition and motor coordination. However, the structure of this complex and its implications for synapse organization and modulation of neurotransmission remain unknown.
The goal of this proposal is to elucidate the molecular architecture of the GluD2–Cerebellin1–Neurexin1β protein complex, and understand its functional implications. I will use X-ray crystallography to obtain high-resolution structural information on binary and ternary complexes between the soluble, extracellular GluD2, Cerebellin1 and Neurexin1β regions. A range of biophysical methods combined with site-directed mutagenesis will be applied to dissect complex formation with respect to affinity, kinetics, stoichiometry and contribution of functional modules. In parallel, using cryo-electron tomography I aim to visualize and reconstruct the higher-order architecture of GluD2–Cerebellin1, and ultimately the trans-synaptic triad, in model cellular membranes. This integrated approach should reveal general principles of supra-molecular organization and function at neuronal synapses, as structurally related molecules are broadly present within the CNS. Understanding synaptic functions in molecular terms will produce enduring paradigms in basic neuroscience and benefit human health.'