Independent regulation of synaptic size and activity by the anaphase-promoting complex.
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.
van Roessel
Peter
P
Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Anatomy, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, United Kingdom.
Elliott
David A
DA
Robinson
Iain M
IM
Prokop
Andreas
A
Brand
Andrea H
AH
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D047908:Intracellular Signaling Peptides and Proteins; D007814:Larva / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D009154:Mutation / Q000235:genetics; D009420:Nervous System / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D011940:Receptor Aggregation / Q000502:physiology; D017470:Receptors, Glutamate / Q000378:metabolism; D013570:Synaptic Membranes / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D025801:Ubiquitin / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; C490600:Liprin-alpha protein, Drosophila; D010750:Phosphoproteins; D017470:Receptors, Glutamate; D025801:Ubiquitin; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome