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The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc

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Show simple item record 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. Waldon, Zachary Chowdhury, Shoaib Worley, Paul F. Steen, Judith Greenberg, Michael E. 2012-10-25T20:30:42Z 2012-10-25T20:30:42Z 2010-03 2009-11
dc.identifier.issn 0092-8674
dc.identifier.issn 1097-4172
dc.description.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. en_US
dc.language.iso en_US
dc.publisher Elsevier en_US
dc.relation.isversionof en_US
dc.rights Creative Commons Attribution-Noncommercial-Share Alike 3.0 en_US
dc.rights.uri en_US
dc.source PMC en_US
dc.title The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc en_US
dc.type Article en_US
dc.identifier.citation Greer, Paul L. et al. “The Angelman Syndrome Protein Ube3A Regulates Synapse Development by Ubiquitinating Arc.” Cell 140.5 (2010): 704–716. en_US
dc.contributor.department Massachusetts Institute of Technology. Department of Biology en_US
dc.contributor.department Whitehead Institute for Biomedical Research en_US
dc.contributor.mitauthor Ploegh, Hidde
dc.contributor.mitauthor Maehr, Rene
dc.relation.journal Cell en_US
dc.identifier.mitlicense OPEN_ACCESS_POLICY en_US
dc.eprint.version Author's final manuscript en_US
dc.type.uri en_US
eprint.status en_US
dspace.orderedauthors Greer, Paul L.; Hanayama, Rikinari; Bloodgood, Brenda L.; Mardinly, Alan R.; Lipton, David M.; Flavell, Steven W.; Kim, Tae-Kyung; Griffith, Eric C.; Waldon, Zachary; Maehr, Rene; Ploegh, Hidde L.; Chowdhury, Shoaib; Worley, Paul F.; Steen, Judith; Greenberg, Michael E. en

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