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Cofilin under control of ?-arrestin-2 in NMDA-dependent dendritic spine plasticity, long-term depression (LTD), and learning.


ABSTRACT: Dendritic spines are dynamic, actin-rich structures that form the postsynaptic sites of most excitatory synapses in the brain. The F-actin severing protein cofilin has been implicated in the remodeling of dendritic spines and synapses under normal and pathological conditions, by yet unknown mechanisms. Here we report that ?-arrestin-2 plays an important role in NMDA-induced remodeling of dendritic spines and synapses via translocation of active cofilin to dendritic spines. NMDAR activation triggers cofilin activation through calcineurin and phosphatidylinositol 3-kinase (PI3K)-mediated dephosphorylation and promotes cofilin translocation to dendritic spines that is mediated by ?-arrestin-2. Hippocampal neurons lacking ?-arrestin-2 develop mature spines that fail to remodel in response to NMDA. ?-Arrestin-2-deficient mice exhibit normal hippocampal long-term potentiation, but significantly impaired NMDA-dependent long-term depression and spatial learning deficits. Moreover, ?-arrestin-2-deficient hippocampal neurons are resistant to A?-induced dendritic spine loss. Our studies demonstrate unique functions of ?-arrestin-2 in NMDAR-mediated dendritic spine and synapse plasticity through spatial control over cofilin activation.

SUBMITTER: Pontrello CG 

PROVIDER: S-EPMC3289389 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Cofilin under control of β-arrestin-2 in NMDA-dependent dendritic spine plasticity, long-term depression (LTD), and learning.

Pontrello Crystal G CG   Sun Min-Yu MY   Lin Alice A   Fiacco Todd A TA   DeFea Kathryn A KA   Ethell Iryna M IM  

Proceedings of the National Academy of Sciences of the United States of America 20120130 7


Dendritic spines are dynamic, actin-rich structures that form the postsynaptic sites of most excitatory synapses in the brain. The F-actin severing protein cofilin has been implicated in the remodeling of dendritic spines and synapses under normal and pathological conditions, by yet unknown mechanisms. Here we report that β-arrestin-2 plays an important role in NMDA-induced remodeling of dendritic spines and synapses via translocation of active cofilin to dendritic spines. NMDAR activation trigg  ...[more]

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