EphrinB2 and GRIP1 stabilize mushroom spines during denervation-induced homeostatic plasticity
- Highlights • Denervation induces mushroom spine loss and AMPAR redistribution to the surface • GRIP1 and ephrinB2 mediate homeostatic mechanisms after lesion • Stimulation with the ephrinB2 receptor EphB4 promotes a surface shift of AMPARs • AMPARs surface shift restores impaired spine recovery after lesion in GRIP1 mutants Summary Despite decades of work, much remains elusive about molecular events at the interplay between physiological and structural changes underlying neuronal plasticity. Here, we combined repetitive live imaging and expansion microscopy in organotypic brain slice cultures to quantitatively characterize the dynamic changes of the intracellular versus surface pools of GluA2-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) across the different dendritic spine types and the shaft during hippocampal homeostatic plasticity. Mechanistically, we identify ephrinB2 and glutamate receptor interacting protein (GRIP) 1 as mediating AMPAR relocation to the mushroom spine surface following lesion-induced denervation. Moreover, stimulation with the ephrinB2 specific receptor EphB4 not only prevents the lesion-induced disappearance of mushroom spines but is also sufficient to shift AMPARs to the surface and rescue spine recovery in a GRIP1 dominant-negative background. Thus, our results unravel a crucial role for ephrinB2 during homeostatic plasticity and identify a potential pharmacological target to improve dendritic spine plasticity upon injury.
Author: | Diane BissenORCiDGND, Maximilian Ken Kracht, Franziska FoßGND, Jan Hofmann, Amparo Acker-PalmerORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-779447 |
DOI: | https://doi.org/10.1016/j.celrep.2021.108923 |
ISSN: | 2211-1247 |
Parent Title (English): | Cell Reports |
Publisher: | Elsevier |
Place of publication: | Amsterdam |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2021/03/30 |
Date of first Publication: | 2021/03/30 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2024/05/16 |
Tag: | AMPA receptors; EphB4; GRIP1; denervation; ephrinB2; expansion microscopy; hippocampus; homeostatic plasticity; mushroom spines; organotypic slice cultures |
Volume: | 34 |
Issue: | 13, art. 108923 |
Article Number: | 108923 |
Page Number: | 27 |
First Page: | 1 |
Last Page: | 11 |
HeBIS-PPN: | 520908473 |
Institutes: | Biowissenschaften / Biowissenschaften |
Angeschlossene und kooperierende Institutionen / MPI für Hirnforschung | |
Fachübergreifende Einrichtungen / Buchmann Institut für Molekulare Lebenswissenschaften (BMLS) | |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Sammlungen: | Universitätspublikationen |
Licence (German): | ![]() |