TY  - JOUR
A1  - Pfennig, Sylvia
A1  - Foß, Franziska
A1  - Bissen, Diane
A1  - Harde, Eva
A1  - Treeck, Julia C.
A1  - Segarra, Marta
A1  - Acker-Palmer, Amparo
T1  - GRIP1 binds to ApoER2 and EphrinB2 to induce activity-dependent AMPA receptor insertion at the synapse
T2  - Cell reports
N2  - 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.
KW  - GRIP1
KW  - AMPA receptors
KW  - synaptic plasticity
KW  - LTP
KW  - ApoER2
KW  - ephrinB
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45557
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-455572
SN  - 2211-1247
N1  - This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
VL  - 21
IS  - 1
SP  - 84
EP  - 96
PB  - Cell Press ; Elsevier
CY  - Maryland Heights, MO ; [New York, NY]
ER  -