The formation of synapses in the central nervous system is controlled through a series of highly coordinated signaling events between the pre- and postsynaptic membrane. The goal of this proposal is to understand the assembly of presynaptic terminals in response to one specific synaptogenic trigger, contact with the postsynaptic adhesion protein Neuroligin. Previous experiments demonstrated that clustering of the axonal neuroligin receptor neurexin results in the formation of functional presynaptic release sites. Moreover, work by others revealed that other components of the presynaptic terminal are not recruited to nascent synapses as individual proteins but in form of large preassembled complexes. Using a combination of dual color timelapse imaging and expression of dominant-negative neurexins in a neuronal culture system I will explore (1) whether the presynaptic adhesion protein neurexin is part of pre-assembled synaptic complexes in axons, (2) how recruitment of synaptic adhesion molecules, active zone components and synaptic vesicles is temporally coordinated and (3) what are the critical protein-protein interactions on the cytoplasmic tail of presynaptic neurexin that result in synapse assembly in response to interaction with postsynaptic neuroligin. ? ?
