SYNAPTIC TARGETING, CLUSTERING AND RELOCALZATION OF GEPHYRIN BY PHOSPHORYLATION, THIOL-MODIFICATION AND CIS-TRANS ISOMERIZATION
Our project investigates the molecular mechanisms controlling the formation, stabilization and dissociation of inhibitory synapses in the central nervous system of vertebrates. The key molecule of inhibitory synapses is gephyrin, a multi-functional and multi-domain scaffolding protein that binds glycine and GABA type A receptors. Gephyrin is targeted by various types of post-translational modifications, that determine the functional state of the protein. The aim of this project is to dissect the functional role phosphorylation, S-palmitoylation and S-nitrosylation on gephyrin oligomerization, receptor clustering and membrane interaction.
Grunewald, N., A. Jan, C. Salvatico, V. Kress, M. Renner, A. Triller, C.G. Specht, and G. Schwarz (2018), Sequences Flanking the Gephyrin-Binding Site of GlyRbeta Tune Receptor Stabilization at Synapses. eNeuro. 5(1).
Kumar, A., B. Dejanovic, F. Hetsch, M. Semtner, D. Fusca, S. Arjune, J.A. SantamariaAraujo, A. Winkelmann, S. Ayton, A.I. Bush, P. Kloppenburg, J.C. Meier, G. Schwarz, and A.A. Belaidi (2017), S-sulfocysteine/NMDA receptor-dependent signaling underlies neurodegeneration in molybdenum cofactor deficiency. J Clinical Investigation. 127(12): p. 4365-4378.
Dejanovic, B., T. Djemie, N. Grunewald, A. Suls, V. Kress, F. Hetsch, D. Craiu, M. Zemel, P. Gormley, D. Lal, E.D.w.g. Euro, C.T. Myers, H.C. Mefford, A. Palotie, I. Helbig, J.C. Meier, P. De Jonghe, S. Weckhuysen, and G. Schwarz (2015), Simultaneous impairment of neuronal and metabolic function of mutated gephyrin in a patient with epileptic encephalopathy. EMBO Mol Med. 7(12): p. 1580-94.