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Ubiquitin ligase RNF167 regulates AMPA receptor-mediated synaptic transmission

Lussier, M. P. and Herring, B. E. and Nasu-Nishimura, Y. and Neutzner, A. and Karbowski, M. and Youle, R. J. and Nicoll, R. A. and Roche, K. W.. (2012) Ubiquitin ligase RNF167 regulates AMPA receptor-mediated synaptic transmission. Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, H. 47. pp. 19426-19431.

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Official URL: http://edoc.unibas.ch/dok/A6338237

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Abstract

AMPA receptors (AMPARs) mediate the majority of fast excitatory neurotransmission, and their density at postsynaptic sites determines synaptic strength. Ubiquitination is a posttranslational modification that dynamically regulates the synaptic expression of many proteins. However, very few of the ubiquitinating enzymes implicated in the process have been identified. In a screen to identify transmembrane RING domain-containing E3 ubiquitin ligases that regulate surface expression of AMPARs, we identified RNF167. Predominantly lysosomal, a subpopulation of RNF167 is located on the surface of cultured neurons. Using a RING mutant RNF167 or a specific shRNA to eliminate endogenous RNF167, we demonstrate that AMPAR surface expression increases in hippocampal neurons with disrupted RNF167 activity and that RNF167 is involved in activity-dependent ubiquitination of AMPARs. In addition, RNF167 regulates synaptic AMPAR currents, whereas synaptic NMDAR currents are unaffected. Therefore, our study identifies RNF167 as a selective regulator of AMPAR-mediated neurotransmission and expands our understanding of how ubiquitination dynamically regulates excitatory synapses.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Ocular Pharmacology and Physiology (Neutzner/Meyer)
UniBasel Contributors:Neutzner, Albert
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:National Academy of Sciences
ISSN:0027-8424
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Apr 2015 09:14
Deposited On:10 Apr 2015 09:14

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