所長招聘セミナー

Dysfunction of a number of molecules implicated in synapse development is linked to many neuropsychiatric disorders including autism and schizophrenia. Synapse development in the brain requires not only physical contact between axons and target neurons but also chemically matched pre- and post-synaptic differentiation. Thus, a synaptic organizing complex, the trans-synaptic adhesion complex that organizes pre- and post-synaptic differentiation, has been suggested to function as the fundamental molecular basis for normal synapse development. The neuroligin-neurexin complex has been the most notable synaptic organizing complex and a genetic determinant predisposing to autism. However, synapse diversity and disease variety suggest many additional trans-synaptic adhesion complexes that organize excitatory and/or inhibitory synapses. For the identification of synaptic organizers that induce presynaptic differentiation, we developed a functional expression screen based on a neuron-fibroblast coculture assay combined with full-length cDNA library or candidate prediction. Further, to identify their presynaptic receptors, we performed candidate cDNA screening based on a binding assay using soluble Fc-fusion recombinant proteins. Through those screens, we found that TrkC-PTPs trans-synaptic complex functions as a bidirectional excitatory synaptic organizing complex. Further, we identified Slitrk3-PTPd trans-synaptic complex as an inhibitory synapse-specific synaptic organizing complex. In this seminar, I will talk about how we identified and characterized TrkC-PTPs complex and Slitrk3-PTPd complex, and discuss about the involvement of those molecules in neuropsychiatric disorders.