期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 7, 页码 E442-E451出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1118803109
关键词
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资金
- National Institutes of Health [MH67121]
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 beta-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 beta-arrestin-2. Hippocampal neurons lacking beta-arrestin-2 develop mature spines that fail to remodel in response to NMDA. beta-Arrestin-2-deficient mice exhibit normal hippocampal long-term potentiation, but significantly impaired NMDA-dependent long-term depression and spatial learning deficits. Moreover, beta-arrestin-2-deficient hippocampal neurons are resistant to A beta-induced dendritic spine loss. Our studies demonstrate unique functions of beta-arrestin-2 in NMDAR-mediated dendritic spine and synapse plasticity through spatial control over cofilin activation.
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