| First Author | Schreiber J | Year | 2015 |
| Journal | J Cell Biol | Volume | 211 |
| Issue | 3 | Pages | 569-86 |
| PubMed ID | 26527743 | Mgi Jnum | J:237577 |
| Mgi Id | MGI:5816193 | Doi | 10.1083/jcb.201506048 |
| Citation | Schreiber J, et al. (2015) Ubiquitin ligase TRIM3 controls hippocampal plasticity and learning by regulating synaptic gamma-actin levels. J Cell Biol 211(3):569-86 |
| abstractText | Synaptic plasticity requires remodeling of the actin cytoskeleton. Although two actin isoforms, beta- and gamma-actin, are expressed in dendritic spines, the specific contribution of gamma-actin in the expression of synaptic plasticity is unknown. We show that synaptic gamma-actin levels are regulated by the E3 ubiquitin ligase TRIM3. TRIM3 protein and Actg1 transcript are colocalized in messenger ribonucleoprotein granules responsible for the dendritic targeting of messenger RNAs. TRIM3 polyubiquitylates gamma-actin, most likely cotranslationally at synaptic sites. Trim3(-/-) mice consequently have increased levels of gamma-actin at hippocampal synapses, resulting in higher spine densities, increased long-term potentiation, and enhanced short-term contextual fear memory consolidation. Interestingly, hippocampal deletion of Actg1 caused an increase in long-term fear memory. Collectively, our findings suggest that temporal control of gamma-actin levels by TRIM3 is required to regulate the timing of hippocampal plasticity. We propose a model in which TRIM3 regulates synaptic gamma-actin turnover and actin filament stability and thus forms a transient inhibitory constraint on the expression of hippocampal synaptic plasticity. |
