Abstract
Neuronal plasticity relies on tightly regulated control of protein levels at synapses. One mechanism to control protein abundance is the ubiquitin-proteasome degradation system. Recent studies have implicated ubiquitin-mediated protein degradation in synaptic development, function, and plasticity, but little is known about the regulatory mechanisms controlling ubiquitylation in neurons. In contrast, ubiquitylation has long been studied as a central regulator of the eukaryotic cell cycle. A critical mediator of cell-cycle transitions, the anaphase-promoting complex/cyclosome (APC/C), is an E3 ubiquitin ligase. Although the APC/C has been detected in several differentiated cell types, a functional role for the complex in postmitotic cells has been elusive. We describe a novel postmitotic role for the APC/C at Drosophila neuromuscular synapses: independent regulation of synaptic growth and synaptic transmission. In neurons, the APC/C controls synaptic size via a downstream effector Liprin-alpha; in muscles, the APC/C regulates synaptic transmission, controlling the concentration of a postsynaptic glutamate receptor.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Anaphase-Promoting Complex-Cyclosome
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Animals
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Drosophila Proteins / metabolism
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Drosophila melanogaster / growth & development*
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Drosophila melanogaster / metabolism
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Drosophila melanogaster / ultrastructure
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Intracellular Signaling Peptides and Proteins
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Larva / growth & development
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Larva / metabolism
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Larva / ultrastructure
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Microscopy, Electron, Transmission
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Mutation / genetics
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Nervous System / growth & development*
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Nervous System / metabolism
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Nervous System / ultrastructure
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Neuromuscular Junction / growth & development*
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Neuromuscular Junction / metabolism
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Neuromuscular Junction / ultrastructure
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Neuronal Plasticity / physiology*
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Phosphoproteins / metabolism
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Receptor Aggregation / physiology
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Receptors, Glutamate / metabolism
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Synaptic Membranes / metabolism
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Synaptic Transmission / physiology
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Ubiquitin / metabolism
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Ubiquitin-Protein Ligase Complexes / genetics
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Ubiquitin-Protein Ligase Complexes / metabolism*
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Up-Regulation / genetics
Substances
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Drosophila Proteins
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Intracellular Signaling Peptides and Proteins
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Liprin-alpha protein, Drosophila
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Phosphoproteins
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Receptors, Glutamate
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Ubiquitin
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Ubiquitin-Protein Ligase Complexes
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Anaphase-Promoting Complex-Cyclosome