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| A study by Matthieu Sainlos and colleagues recently published in "Nature Chemical Biology". "Biomimetic divalent ligands for the acute disruption of synaptic AMPARstabilization." M Sainlos C Tigaret, C Poujol, N Olivier, L Bard, C Breillat, K Thiolon, D Choquet, B Imperiali. Nature Chemical Biology Published on line December 26, 2010, |
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Since 2008 Matthieu Sainlos is CNRS research scientist in Daniel Choquet group (IINS, CNRS UMR 5297) |
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| Matthieu Sainlos Researcher; PhD CNRS Program areas: Synapse FENS Themes Synaptic transmission and excitability / Synaptic plasticity Scientific expertise protein/protein interactions ; bioorganic chemistry ; protein and peptide chemistry ; molecular biology ; biochemistry ; structural biology Technical expertise: organic and peptide synthesis ; recombinant protein ; spectroscopy Keywords: chemical probes ; MAGUK proteins (membrane associated guanylate kinase) ; PDZ domains |
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| Downloading plugin Falsh Player / Music ©Jean Eberlé |
Video time 5' | January 12, 2011 | |
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The interactions of the AMPA receptor (AMPAR) auxiliary subunit Stargazin with PDZ domain–containing scaffold proteins such as PSD-95 are critical for the synaptic stabilization of AMPARs. To investigate these interactions, we have developed biomimetic competing ligands that are assembled from two Stargazin-derived PSD-95/DLG/ZO-1 (PDZ) domain–binding motifs using 'click' chemistry. Characterization of the ligands in vitro and in a cellular FRET-based model revealed an enhanced affinity for the multiple PDZ domains of PSD-95 compared to monovalent peptides. In cultured neurons, the divalent ligands competed with transmembrane AMPAR regulatory protein (TARP) for the intracellular membrane-associated guanylate kinase resulting in increased lateral diffusion and endocytosis of surface AMPARs, while showing strong inhibition of synaptic AMPAR currents. This provides evidence for a model in which the TARP-containing AMPARs are stabilized at the synapse by engaging in multivalent interactions. In light of the prevalence of PDZ domain clusters, these new biomimetic chemical tools could find broad application for acutely perturbing multivalent complexes. In french on the CNRS website....clic |
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| Read more... Bard L, Sainlos M, Bouchet D, Cousins S, Mikasova L, Breillat C, Stephenson FA, Imperiali B, Choquet D, Groc L. Dynamic and specific interaction between synaptic NR2-NMDA receptor and PDZ proteins. P Natl Acad Sci USA. 2010 Oct 25. 2010 Lucie Bard thesis, click... Laurent Groc HDR, click.. |
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| Communication INB / Yves Deris January 11, 2010 |
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