Triad3A regulates synaptic strength by ubiquitination of Arc.

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.

• Authors: Angela M Mabb, H Shawn Je, Mark J Wall, Camenzind G Robinson, Rylan S Larsen, Yuan Qiang, Sonia A L Corrêa, Michael D Ehlers
• Journal: Neuron (Neuron) Vol. 82 Issue 6 Pg. 1299-316 (Jun 18 2014) ISSN: 1097-4199 [Electronic] United States
• PMID: 24945773 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Clathrin
• Cytoskeletal Proteins
• Nerve Tissue Proteins
• activity regulated cytoskeletal-associated protein
• RNF216 protein, human
• Ubiquitin-Protein Ligases

Topics

• Clathrin (physiology)
• Cytoskeletal Proteins (metabolism)
• Excitatory Postsynaptic Potentials (physiology)
• HEK293 Cells
• Humans
• Nerve Tissue Proteins (metabolism)
• Synapses (physiology)
• Ubiquitin-Protein Ligases (physiology)
• Ubiquitination (physiology)