The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc
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Ploegh_The Angelman.pdf
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Author(s)
Ploegh, Hidde
Maehr, Rene
Greer, Paul L.
Hanayama, Rikinari
Bloodgood, Brenda L.
Mardinly, Alan R.
Lipton, David M.
Flavell, Steven W.
Kim, Tae-Kyung
Griffith, Eric C.
Date Issued
March 2010
Journal
Cell
Publisher
Elsevier
Citation
Greer, Paul L. et al. “The Angelman Syndrome Protein Ube3A Regulates Synapse Development by Ubiquitinating Arc.” Cell 140.5 (2010): 704–716.
Version
Author's final manuscript
Abstract
Angelman Syndrome is a debilitating neurological disorder caused by mutation of the E3 ubiquitin ligase Ube3A, a gene whose mutation has also recently been associated with autism spectrum disorders (ASDs). The function of Ube3A during nervous system development and how Ube3A mutations give rise to cognitive impairment in individuals with Angleman Syndrome and ASDs are not clear. We report here that experience-driven neuronal activity induces Ube3A transcription and that Ube3A then regulates excitatory synapse development by controlling the degradation of Arc, a synaptic protein that promotes the internalization of the AMPA subtype of glutamate receptors. We find that disruption of Ube3A function in neurons leads to an increase in Arc expression and a concomitant decrease in the number of AMPA receptors at excitatory synapses. We propose that this deregulation of AMPA receptor expression at synapses may contribute to the cognitive dysfunction that occurs in Angelman Syndrome and possibly other ASDs.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Creative Commons Attribution-Noncommercial-Share Alike 3.0
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DOI of Published Version
https://doi.org/10.1016/j.cell.2010.01.026
