Independent Regulation of Synaptic Size and Activity by the Anaphase-Promoting Complex

• Published in: Cell 2004-11, Vol.119 (5), p.707-718
• Main Authors: van Roessel, Peter, Elliott, David A., Robinson, Iain M., Prokop, Andreas, Brand, Andrea H.
• Format: Article
• Language: English
• Subjects: Anaphase-Promoting Complex-Cyclosome; Animals; Drosophila; Drosophila melanogaster - growth & development; Drosophila melanogaster - metabolism; Drosophila melanogaster - ultrastructure; Drosophila Proteins - metabolism; Larva - growth & development; Larva - metabolism; Larva - ultrastructure; Microscopy, Electron, Transmission; Mutation - genetics; Nervous System - growth & development; Nervous System - metabolism; Nervous System - ultrastructure; Neuromuscular Junction - growth & development; Neuromuscular Junction - metabolism; Neuromuscular Junction - ultrastructure; Neuronal Plasticity - physiology; Phosphoproteins - metabolism; Receptor Aggregation - physiology; Receptors, Glutamate - metabolism; Synaptic Membranes - metabolism; Synaptic Transmission - physiology; Ubiquitin - metabolism; Ubiquitin-Protein Ligase Complexes - genetics; Ubiquitin-Protein Ligase Complexes - metabolism; Up-Regulation - genetics
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2004.11.028

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-α; in muscles, the APC/C regulates synaptic transmission, controlling the concentration of a postsynaptic glutamate receptor.