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Triad3A regulates synaptic strength by ubiquitination of Arc
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Mabb, Angela M., Je, H. Shawn, Wall, Mark J., Robinson, Camenzind G., Larsen, Rylan S., Qiang, Yuan, Corrêa, Sônia A. L. and Ehlers, Michael D. (2014) Triad3A regulates synaptic strength by ubiquitination of Arc. Neuron, Volume 82 (Number 6). pp. 1299-1316. doi:10.1016/j.neuron.2014.05.016 ISSN 0896-6273.
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Official URL: http://dx.doi.org/10.1016/j.neuron.2014.05.016
Abstract
Activity-dependent gene transcription and protein synthesis underlie many forms of learning-related synaptic plasticity. At excitatory glutamatergic synapses, the immediate early gene product Arc/Arg3.1 couples synaptic activity to postsynaptic endocytosis of AMPA-type glutamate receptors. Although the mechanisms for Arc induction have been described, little is known regarding the molecular machinery that terminates Arc function. Here, we demonstrate that the RING domain ubiquitin ligase Triad3A/RNF216 ubiquitinates Arc, resulting in its rapid proteasomal degradation. Triad3A associates with Arc, localizes to clathrin-coated pits, and is associated with endocytic sites in dendrites and spines. In the absence of Triad3A, Arc accumulates, leading to the loss of surface AMPA receptors. Furthermore, loss of Triad3A mimics and occludes Arc-dependent forms of synaptic plasticity. Thus, degradation of Arc by clathrin-localized Triad3A regulates the availability of synaptic AMPA receptors and temporally tunes Arc-mediated plasticity at glutamatergic synapses.
| Item Type: | Journal Article | ||||||
|---|---|---|---|---|---|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||
| Journal or Publication Title: | Neuron | ||||||
| Publisher: | Cell Press | ||||||
| ISSN: | 0896-6273 | ||||||
| Official Date: | 18 June 2014 | ||||||
| Dates: |
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| Volume: | Volume 82 | ||||||
| Number: | Number 6 | ||||||
| Page Range: | pp. 1299-1316 | ||||||
| DOI: | 10.1016/j.neuron.2014.05.016 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Open Access (Creative Commons) |
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