γ-Secretase promotes Drosophila Postsynaptic Development Through the Cleavage of a Wnt Receptor
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 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 and suggests that receptor processing by proteins linked to neurodegeneration may be a shared mechanism with aspects of synaptic development.
Restrepo, Lucas J; DePew, Alison T; Moese, Elizabeth R; Tymanskyj, Stephen R; Parisi, Michael J; Aimino, Michael A; Duhart, Juan Carlos; Fei, Hong; and Mosca, Timothy J, "γ-Secretase promotes Drosophila Postsynaptic Development Through the Cleavage of a Wnt Receptor" (2022). Farber Institute for Neuroscience Faculty Papers. Paper 44.
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This article is the author's final published version in Developmental Cell, Volume 57, Issue 13, July 2022, Pages 1643 - 1660.e7.
The published version is available at https://doi.org/10.1016/j.devcel.2022.05.006.
Copyright © 2022 The Author(s).
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)