Cooperation of synaptic adhesion molecules in synapse formation and function

• Applicant: Professor Dr. Kurt Gottmann
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2012 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 218389339

Synaptic cell adhesion molecules (SCAMs) mediate transsynaptic signaling by protein-protein interactions across the synaptic cleft. SCAM signaling is thought to control synapse formation and maturation, and to be involved in neurological diseases. Several diverse types of SCAMs have been characterized at the molecular level. However, how they cooperate with each other to achieve the precise regulation of synapse formation and function is largely unknown. We will mainly focus on the cooperation of N-cadherin and Neuroligin-1 that has recently been found by our group (Stan et al., 2010). We will analyse this cooperation at nascent synapses to molecularly understand its role in synaptic vesicle accumulation. Neuroligin-1 function will be studied in conditional N-cadherin knockout neurons, and upon RNA interference-mediated knockdown of catenins and postsynaptic scaffolding proteins. In addition, a potential crossregulatory role of signaling cascades, e.g. Wnt signaling will be addressed. To learn how NMDA receptors are modulating SCAM activity, we will study the influence of NMDA receptor activity on the N-cadherin Neuroligin-1 cooperation. To further address whether cooperation mechanisms are of general importance for SCAM function, we will investigate whether other SCAMs (SynCAMs; LRRTMs) also require a cooperation with N-cadherin. In addition to nascent synapses, we will study the cooperation of N-cadherin and Neuroligin-1 at fully functional, mature glutamatergic synapses. We will use an electrophysiological approach to analyse the molecular mechanisms (involvement of N-cadherin) underlying the modulation of presynaptic release probability by Neuroligin-1.

• DFG Programme: Research Grants