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Regulation of molecular interactions between synaptic components

Head of Project : Christian Specht

Single molecule localisation microscopy (SMLM) gives access to spatio-temporal distribution patterns that reflect the molecular interactions in which the proteins engage : we can count the number and density of molecules in specific compartments, visualise their localisation with high spatial precision, and track their movements at high temporal resolution in living cells. The comparison with biochemical approaches shows that the mobility of cellular components is inversely related to the binding constants of purified proteins, demonstrating that SMLM data can yield information about molecular interactions in living cells.

Changes in the number or the binding properties of synaptic proteins necessarily alter the organisation of the synaptic structure, which in turn affects the efficacy of synaptic transmission. Using SMLM strategies our project explores the interactions between membrane receptors, scaffold and adhesion proteins as well as signalling and cytoskeletal elements at synapses. We investigate how the binding properties of different pre- and postsynaptic components are regulated through network activity and signalling processes in cultured neurons and organotypic slices.

Participants : C. Specht, X. Yang, A. Jan, F. Niwa, and N. Frézel

Grünewald N, Jan A, Salvatico C, Kress V, Renner R, Triller A, Specht CG, Schwarz G (2018). Sequences flanking the gephyrin-binding site of GlyR-beta tune receptor stabilization at synapses. eNeuro.

Patrizio A, Renner M, Pizzarelli R, Triller A, Specht CG (2017). Alpha subunit-dependent glycine receptor clustering and regulation of synaptic receptor numbers. Sci Rep 7:10899.

Salvatico C, Specht CG and Triller A (2015). Synaptic receptor dynamics : from theoretical concepts to deep quantification and chemistry in cellulo. Neuropharmacol 88:2-9.

Specht CG, Izeddin I, Rodriguez PC, El Beheiry M, Rostaing P, Darzacq X, Dahan M and Triller A (2013). Quantitative nanoscopy of inhibitory synapses : counting gephyrin molecules and receptor binding sites. Neuron 79:308-321.