18 Oral - Neurodevelopment I
Thursday April 07, 5:00 PM - 5:15 PM

Authors:
Lucas Restrepo; Alison DePew; Elizabeth Moese; Stephen Tymanskyj; Michael Parisi; Michael Aimino; Juan Duhart; Hong Fei; Timothy Mosca

Affiliation: Department of Neuroscience, Thomas Jefferson University, Philadelphia, PA USA

Keywords:
c. synaptogenesis; e. synaptic function and organization

Developing synapses mature through the recruitment of specific proteins that stabilize pre- and post-synaptic structure and function. Wnt ligands signaling via Frizzled (Fz) receptors play many crucial roles in neuronal and synaptic development but whether and how Wnt and Fz influence synaptic maturation is incompletely understood. We demonstrate that Fz2 receptor cleavage via the γ-secretase complex is required for postsynaptic development and maturation. In the absence of γ-secretase, Drosophila neuromuscular synapses fail to recruit postsynaptic scaffolding and cytoskeletal proteins, leading to behavioral deficits. Strikingly, introducing γ-secretase mutations linked to familial early-onset Alzheimer’s Disease into flies leads to synaptic maturation phenotypes that are identical to those seen in null alleles. This conserved role for γ-secretase in synaptic maturation and postsynaptic development highlights the importance of Fz2 cleavage, identifies its mechanism, and suggests that receptor processing by proteins linked to neurodegeneration may be a shared mechanism affecting aspects of synaptic development.