| First Author | Pontrello CG | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 7 | Pages | E442-51 |
| PubMed ID | 22308427 | Mgi Jnum | J:182613 |
| Mgi Id | MGI:5316171 | Doi | 10.1073/pnas.1118803109 |
| Citation | Pontrello CG, et al. (2012) Cofilin under control of beta-arrestin-2 in NMDA-dependent dendritic spine plasticity, long-term depression (LTD), and learning. Proc Natl Acad Sci U S A 109(7):E442-51 |
| abstractText | 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 Abeta-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. |
