GRIP1 binds to ApoER2 and EphrinB2 to induce activity-dependent AMPA receptor insertion at the synapse

Regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking in response to neuronal activity is critical for synaptic function and plasticity. Here, we show that neuronal activity induc
Regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking in response to neuronal activity is critical for synaptic function and plasticity. Here, we show that neuronal activity induces the binding of ephrinB2 and ApoER2 receptors at the postsynapse to regulate de novo insertion of AMPA receptors. Mechanistically, the multi-PDZ adaptor glutamate-receptor-interacting protein 1 (GRIP1) binds ApoER2 and bridges a complex including ApoER2, ephrinB2, and AMPA receptors. Phosphorylation of ephrinB2 in a serine residue (Ser-9) is essential for the stability of such a complex. In vivo, a mutation on ephrinB2 Ser-9 in mice results in a complete disruption of the complex, absence of ApoER2 downstream signaling, and impaired activity-induced and ApoER2-mediated AMPA receptor insertion. Using compound genetics, we show the requirement of this complex for long-term potentiation (LTP). Together, our findings uncover a cooperative ephrinB2 and ApoER2 signaling at the synapse, which serves to modulate activity-dependent AMPA receptor dynamic changes during synaptic plasticity.
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Metadaten
Author:Sylvia Pfennig, Franziska Foss, Diane Bissen, Eva Harde, Julia C. Treeck, Marta Segarra, Amparo Acker-Palmer
URN:urn:nbn:de:hebis:30:3-455572
DOI:http://dx.doi.org/10.1016/j.celrep.2017.09.019
ISSN:2211-1247
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=28978486
Parent Title (English):Cell reports
Publisher:Cell Press ; Elsevier
Place of publication:Maryland Heights, MO ; [New York, NY]
Document Type:Article
Language:English
Year of Completion:2017
Date of first Publication:2017/10/03
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/01/30
Tag:AMPA receptors; ApoER2; GRIP1; LTP; ephrinB; synaptic plasticity
Volume:21
Issue:1
Pagenumber:14
First Page:84
Last Page:96
Note:
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
HeBIS PPN:426718704
Institutes:Biowissenschaften
Exzellenzcluster Makromolekulare Komplexe
Dewey Decimal Classification:570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0

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