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Γ-Secretase Promotes Drosophila Postsynaptic Development Through The Cleavage Of A Wnt Receptor, Lucas J Restrepo, Alison T Depew, Elizabeth R Moese, Stephen R Tymanskyj, Michael J Parisi, Michael A Aimino, Juan Carlos Duhart, Hong Fei, Timothy J Mosca

Farber Institute for Neuroscience Faculty Papers

Developing synapses mature through the recruitment of specific proteins that stabilize presynaptic and postsynaptic 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. Here, we show 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. Introducing presenilin mutations linked to familial early-onset Alzheimer's disease into flies leads to synaptic maturation phenotypes …