Skip to main content
European Commission logo
italiano italiano
CORDIS - Risultati della ricerca dell’UE
CORDIS
CORDIS Web 30th anniversary CORDIS Web 30th anniversary
Contenuto archiviato il 2024-06-18

Chemical biology approach to study the role of PDZ domain-mediated interactions in synaptic plasticity

Obiettivo

Complex dynamic protein-protein interactions are the base of protein-based networks in cells. Among them, the synaptic connection between two neurons is one of the most challenging. The postsynaptic density (PSD) at excitatory synapses in the brain is a prototypical example of protein-based network whose nanoscale structure and composition determines cellular function. Moreover, dynamic regulation of PSD composition and receptor movement into or out of the PSD is the base of current molecular theories of learning and memory. However, the nature of this regulation remains poorly understood partly due to the lack of tools that would allow disruption and control of specific interactions.
Several key components of the PSD such as PSD-95 contain multiple PDZ domains and the interactions mediated by these small domains are involved in critical events such as synaptic targeting and anchoring of glutamate receptors (AMPARs, NMDARs). The aim of this project is to design and exploit original tools to better understand the role of PDZ domain-mediated interactions in the context of synaptic plasticity by employing a chemical biology approach associating synthesis, biophysical measurements and live cell studies. In particular two different aspects will be addressed: 1) development of efficient and specific competing biomimetic ligands that integrate the multivalent nature of these interactions and 2) spatio-temporal control of the disruption of these PDZ domain-mediated interactions by incorporating to the previous ligands photolabile caging groups. The specific targets comprise on the one hand the main synaptic PDZ domain-containing scaffolding proteins (PSD-95, SAP97, PSD-93 and SAP102) and on the other AMPA and NMDA receptor complexes. Finally, these tools will complement common biological approaches by allowing us to study localized and dynamic macromolecular events between endogenous proteins.

Invito a presentare proposte

FP7-PEOPLE-2010-IEF
Vedi altri progetti per questo bando

Coordinatore

UNIVERSITE VICTOR SEGALEN BORDEAUX II
Contributo UE
€ 185 248,00
Indirizzo
RUE LEO SAIGNAT 146
33076 BORDEAUX CEDEX
Francia

Mostra sulla mappa

Tipo di attività
Higher or Secondary Education Establishments
Contatto amministrativo
Daniel Choquet (Dr.)
Collegamenti
Costo totale
Nessun dato