期刊
JOURNAL OF NEUROSCIENCE
卷 41, 期 14, 页码 3068-3081出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2472-20.2021
关键词
Abl2; actin; cortactin; dendritic spine stability; FRAP; stable actin
资金
- National Institutes of Health [NS089662, NS105640, MH115939, F31 MH116571, T32GM007223]
Dendritic spines are enriched in a network of actin filaments, with stable actin filaments maintained by interactions between Abl2 and cortactin being crucial for spine stability. Disruption of these interactions leads to reduced spine density and impaired spine stability, while increased synaptic activity can rescue spine loss by promoting cortactin enrichment in vulnerable spines.
Dendritic spines act as the receptive contacts at most excitatory synapses. Spines are enriched in a network of actin filaments comprised of two kinetically distinct pools. The majority of spine actin is highly dynamic and regulates spine size, structural plasticity, and postsynaptic density organization. The remainder of the spine actin network is more stable, but the function of this minor actin population is not well understood, as tools to study it have not been available. Previous work has shown that disruption of the Abl2/Arg nonreceptor tyrosine kinase in mice compromises spine stability and size. Here, using cultured hippocampal neurons pooled from both sexes of mice, we provide evidence that binding to cortactin tethers Abl2 in spines, where Abl2 and cortactin maintain the small pool of stable actin required for dendritic spine stability. Using fluorescence recovery after photobleaching of GFP-actin, we find that disruption of Abl2:cortactin interactions eliminates stable actin filaments in dendritic spines, significantly reducing spine density. A subset of spines remaining after Abl2 depletion retain their stable actin pool and undergo activity-dependent spine enlargement, associated with increased cortactin and GluN2B levels. Finally, tonic increases in synaptic activity rescue spine loss following Abl2 depletion by promoting cortactin enrichment in vulnerable spines. Together, our findings strongly suggest that Abl2:cortactin interactions promote spine stability by maintaining pools of stable actin filaments in spines.
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