| First Author | Klein ME | Year | 2015 |
| Journal | Cell Rep | PubMed ID | 25753412 |
| Mgi Jnum | J:228193 | Mgi Id | MGI:5705481 |
| Doi | 10.1016/j.celrep.2015.02.020 | Citation | Klein ME, et al. (2015) Coordination between Translation and Degradation Regulates Inducibility of mGluR-LTD. Cell Rep |
| abstractText | Dendritic protein homeostasis is crucial for most forms of long-term synaptic plasticity, and its dysregulation is linked to a wide range of brain disorders. Current models of metabotropic glutamate receptor mediated long-term depression (mGluR-LTD) suggest that rapid, local synthesis of key proteins is necessary for the induction and expression of LTD. Here, we find that mGluR-LTD can be induced in the absence of translation if the proteasome is concurrently inhibited. We report that enhanced proteasomal degradation during the expression of mGluR-LTD depletes dendritic proteins and inhibits subsequent inductions of LTD. Moreover, proteasome inhibition can rescue mGluR-LTD in mice null for the RNA binding protein Sam68, which we show here lack mGluR-dependent translation and LTD. Our study provides mechanistic insights for how changes in dendritic protein abundance regulate mGluR-LTD induction. We propose that Sam68-mediated translation helps to counterbalance degradation, ensuring that protein levels briefly remain above a permissive threshold during LTD induction. |
