Fz2 receptor cleavage promotes postsynaptic maturation at the Drosophila NMJ
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Postsynaptic γ-secretase in development regulates synaptic maturation and function
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γ-secretase influences postsynaptic maturation by enabling the cleavage of Fz2
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AD-linked alleles of presenilin in fly show synaptic maturation defects
Summary
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.
Graphical abstract
Keywords
synapse
neurobiology
Drosophila
neuromuscular junction
Wnt
Frizzled
synapse maturation
presenilin
γ-secretase
Alzheimer's Disease
Data and code availability
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Original data including image files, Western blots, or data tables are available from the lead contact on reasonable request.
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No new code was created for this study.
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Any additional information required to repeat the experiments or reanalyze the data is available from the lead contact on reasonable request.