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  AMPA receptor signaling through BRAG2 and Arf6 critical for long-term synaptic depression

Scholz, R., Berberich, S., Rathgeber, L., Kolleker, A., Köhr, G., & Kornau, H. C. (2010). AMPA receptor signaling through BRAG2 and Arf6 critical for long-term synaptic depression. Neuron, 66(5), 768-780. doi:10.1016/j.neuron.2010.05.003.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-5D88-9 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-5D89-7
Genre: Journal Article
Alternative Title : AMPA receptor signaling through BRAG2 and Arf6 critical for long-term synaptic depression

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Neuron_66_2010_768.pdf (Any fulltext), 748KB
 
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 Creators:
Scholz, Ralf, Author
Berberich, Sven1, Author              
Rathgeber, Louisa, Author
Kolleker, Aleksandre1, Author              
Köhr, Georg1, Author              
Kornau, Hans Christian1, Author              
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              

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Free keywords: MOLNEURO; SIGNALING
 Abstract: Central nervous system synapses undergo activity-dependent alterations to support learning and memory. Long-term depression (LTD) reflects a sustained reduction of the synaptic AMPA receptor content based on targeted clathrin-mediated endocytosis. Here we report a current-independent form of AMPA receptor signaling, fundamental for LTD. We found that AMPA receptors directly interact via the GluA2 subunit with the synaptic protein BRAG2, which functions as a guanine-nucleotide exchange factor (GEF) for the coat-recruitment GTPase Arf6. BRAG2-mediated catalysis, controlled by ligand-binding and tyrosine phosphorylation of GluA2, activates Arf6 to internalize synaptic AMPA receptors upon LTD induction. Furthermore, acute blockade of the GluA2-BRAG2 interaction and targeted deletion of BRAG2 in mature hippocampal CA1 pyramidal neurons prevents LTD in CA3-to-CA1 cell synapses, irrespective of the induction pathway. We conclude that BRAG2-mediated Arf6 activation triggered by AMPA receptors is the convergent step of different forms of LTD, thus providing an essential mechanism for the control of vesicle formation by endocytic cargo.

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Language(s): eng - English
 Dates: 2010-04-212010-06-092010-06-10
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 664586
DOI: 10.1016/j.neuron.2010.05.003
URI: https://www.ncbi.nlm.nih.gov/pubmed/20547133
Other: 7578
 Degree: -

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Title: Neuron
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 66 (5) Sequence Number: - Start / End Page: 768 - 780 Identifier: ISSN: 0896-6273
CoNE: https://pure.mpg.de/cone/journals/resource/954925560565