| First Author | Oudart M | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 5 | Pages | 112456 |
| PubMed ID | 37126448 | Mgi Jnum | J:337577 |
| Mgi Id | MGI:7491462 | Doi | 10.1016/j.celrep.2023.112456 |
| Citation | Oudart M, et al. (2023) The ribosome-associated protein RACK1 represses Kir4.1 translation in astrocytes and influences neuronal activity. Cell Rep 42(5):112456 |
| abstractText | The regulation of translation in astrocytes, the main glial cells in the brain, remains poorly characterized. We developed a high-throughput proteomics screen for polysome-associated proteins in astrocytes and focused on ribosomal protein receptor of activated protein C kinase 1 (RACK1), a critical factor in translational regulation. In astrocyte somata and perisynaptic astrocytic processes (PAPs), RACK1 preferentially binds to a number of mRNAs, including Kcnj10, encoding the inward-rectifying potassium (K(+)) channel Kir4.1. By developing an astrocyte-specific, conditional RACK1 knockout mouse model, we show that RACK1 represses production of Kir4.1 in hippocampal astrocytes and PAPs. Upregulation of Kir4.1 in the absence of RACK1 increases astrocytic Kir4.1-mediated K(+) currents and volume. It also modifies neuronal activity attenuating burst frequency and duration. Reporter-based assays reveal that RACK1 controls Kcnj10 translation through the transcript's 5' untranslated region. Hence, translational regulation by RACK1 in astrocytes represses Kir4.1 expression and influences neuronal activity. |
