Objectif The proper coupling between presynaptic and postsynaptic neurons is essential for synaptic signalling. Synapse formation, maturation, and maintenance are controlled by cell adhesion systems that recruit and organise the synaptic protein machinery. One such system comprises presynaptic neurexins and postsynaptic neuroligins. Of the five known neuroligins, neuroligin 1 is specific for excitatory synapses, while neuroligin 2 is specific for inhibitory synapses and Neuroligin 3 is found on both excitatory and inhibitory synapses. The synaptic localisation of neuroligins 4 and 5 is unknown.The neuroligin/neurexin system is critically involved in the accumulation of scaffold and receptor proteins at postsynapses. However, the mechanisms by which this protein recruitment proceeds are still largely unknown. Loss of neuroligins and dysfunction of the neuroligin/neurexin system are associated with synaptic defects in vitro and in vivo, and mutations in neuroligin 3 or 4 cause monogenic forms of autism spectrum disorders (ASD) in humans. Correspondingly, neuroligin 4 deficient mice show social interaction and communication deficits that are reminiscent of ASD.In this study, I will employ a wide spectrum of genetic, biochemical, cell biological, and electrophysiological methods in combination with mice lacking one or multiple neuroligins to (1) identify novel neuroligin interactors, to (2) characterise functional interactions and redundancies among neuroligins and other adhesion proteins with regard to synapse formation, function, and plasticity, and to (3) generate a conditional knock-in mouse for neuroligin 4 and study the autistic phenotype and behavioural responses in the mature brain. These studies will aid in elucidating the function of the neuroligin/neurexin system in the normal brain as well as in synaptopathic conditions, such as ASD, in which the function of the neuroligin/neurexin system is perturbed. Champ scientifique natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencescell biologynatural sciencesbiological sciencesgeneticsmutation Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2010-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Appel à propositions FP7-PEOPLE-2010-IEF Voir d’autres projets de cet appel Régime de financement MC-IEF - Intra-European Fellowships (IEF) Coordinateur MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Contribution de l’UE € 162 742,40 Adresse HOFGARTENSTRASSE 8 80539 Munchen Allemagne Voir sur la carte Région Bayern Oberbayern München, Kreisfreie Stadt Type d’activité Research Organisations Contact administratif Nils Brose (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
