| The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc. | |
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MedLine Citation:
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PMID: 20211139 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Paul L Greer; Rikinari Hanayama; Brenda L Bloodgood; Alan R Mardinly; David M Lipton; Steven W Flavell; Tae-Kyung Kim; Eric C Griffith; Zachary Waldon; Rene Maehr; Hidde L Ploegh; Shoaib Chowdhury; Paul F Worley; Judith Steen; Michael E Greenberg |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Cell Volume: 140 ISSN: 1097-4172 ISO Abbreviation: Cell Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-09 Completed Date: 2010-03-30 Revised Date: 2011-07-26 |
Medline Journal Info:
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Nlm Unique ID: 0413066 Medline TA: Cell Country: United States |
Other Details:
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Languages: eng Pagination: 704-16 Citation Subset: IM |
Copyright Information:
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(c) 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angelman Syndrome
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physiopathology* Animals Cells, Cultured Cognition Cytoskeletal Proteins / metabolism* Humans Mice Mice, Knockout Nerve Tissue Proteins / metabolism* Receptors, AMPA / metabolism Synapses / metabolism Ubiquitin-Protein Ligases / metabolism* Ubiquitination |
| Grant Support | |
ID/Acronym/Agency:
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MH53608/MH/NIMH NIH HHS; NS28829/NS/NINDS NIH HHS; R01 NS028829-19/NS/NINDS NIH HHS; R01 NS028829-20/NS/NINDS NIH HHS; R01 NS028829-21/NS/NINDS NIH HHS; R01 NS028829-21S1/NS/NINDS NIH HHS; R01 NS028829-23/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytoskeletal Proteins; 0/Nerve Tissue Proteins; 0/Receptors, AMPA; 0/activity regulated cytoskeletal-associated protein; EC 6.3.2.19/Ube3a protein, mouse; EC 6.3.2.19/Ubiquitin-Protein Ligases |
| Comments/Corrections | |
Comment In:
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Nat Rev Neurosci. 2010 May;11(5):298
[PMID:
20419861
]
Cell. 2010 Mar 5;140(5):608-10 [PMID: 20211128 ] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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