β-Amyloid disruption of LTP/LTD balance is mediated by AKAP150-anchored PKA and Calcineurin regulation of Ca2+-permeable AMPA receptors
In: Cell reports, Jg. 37 (2021), Heft 1, S. 109786-109786
Online
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Zugriff:
SUMMARY Regulated insertion and removal of postsynaptic AMPA glutamate receptors (AMPARs) mediates hippocampal long-term potentiation (LTP) and long-term depression (LTD) synaptic plasticity underlying learning and memory. In Alzheimer’s disease β-amyloid (Aβ) oligomers may impair learning and memory by altering AMPAR trafficking and LTP/LTD balance. Importantly, Ca2+-permeable AMPARs (CP-AMPARs) assembled from GluA1 subunits are excluded from hippocampal synapses basally but can be recruited rapidly during LTP and LTD to modify synaptic strength and signaling. By employing mouse knockin mutations that disrupt anchoring of the kinase PKA or phosphatase Calcineurin (CaN) to the postsynaptic scaffold protein AKAP150, we find that local AKAP-PKA signaling is required for CP-AMPAR recruitment, which can facilitate LTP but also, paradoxically, prime synapses for Aβ impairment of LTP mediated by local AKAP-CaN LTD signaling that promotes subsequent CP-AMPAR removal. These findings highlight the importance of PKA/CaN signaling balance and CP-AMPARs in normal plasticity and aberrant plasticity linked to disease.
Graphical Abstract
In brief In Alzheimer’s disease, Aβ oligomers disrupt hippocampal neuronal plasticity and cognition. Sanderson et al. show how the postsynaptic scaffold protein AKAP150 coordinates PKA and Calcineurin regulation of Ca2+-permeable AMPA-type glutamate receptors to mediate disruption of synaptic plasticity by Aβ oligomers.
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β-Amyloid disruption of LTP/LTD balance is mediated by AKAP150-anchored PKA and Calcineurin regulation of Ca2+-permeable AMPA receptors
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Autor/in / Beteiligte Person: | Gorski, Jessica A. ; Dell'Acqua, Mark L. ; Sanderson, Jennifer L. ; Freund, Ronald K. |
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Zeitschrift: | Cell reports, Jg. 37 (2021), Heft 1, S. 109786-109786 |
Veröffentlichung: | 2021 |
Medientyp: | unknown |
ISSN: | 2211-1247 (print) |
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