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Fluorescent caged phosphopeptides as probes to investigate glutamate receptors trafficking at the synapse level by time and site specific modifications of PICK-AMPAR interactions

Ziel

The aim of this project is to devise new chemical probes to investigate specific protein-protein interactions in neurons. The probes include caged phosphopeptides, which are fluorescently labelled to enable, for the first time, site and time specific perturbation of receptor trafficking and stabilisation at the level of individual synapses.

This project represents a unique combination of advanced chemistry with high-resolution imaging. We will concentrate on processes involved in the regulation of synaptic transmission at excitatory glutamatergic synapses. Namely, the main focus will be on interfering with the interaction between AMPA type glutamate receptors and the associated scaffold proteins PICK and GRIP. Phosphorylation dependent regulation of this interaction is indeed emerging as a key player in the processes of synaptic plasticity thought to underlie learning and memory.

The first goal of the work in the Imperiali laboratory will involve synthesis of a family of fluorescently labelled caged phosphopep tides. The tools developed in the Imperiali group will then be used in the Choquet laboratory to investigate the rules underlying receptor trafficking in multiphoton and single molecule imaging experiments combined with electrophysiological recordings of synaptic transmission.

Aufforderung zur Vorschlagseinreichung

FP6-2002-MOBILITY-6
Andere Projekte für diesen Aufruf anzeigen

Koordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
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