1. The ribosome-associated protein RACK1 represses Kir4.1 translation in astrocytes and influences neuronal activity
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Marc Oudart, Katia Avila-Gutierrez, Clara Moch, Elena Dossi, Giampaolo Milior, Anne-Cécile Boulay, Mathis Gaudey, Julien Moulard, Bérangère Lombard, Damarys Loew, Alexis-Pierre Bemelmans, Nathalie Rouach, Clément Chapat, and Martine Cohen-Salmon
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CP: Neuroscience ,Biology (General) ,QH301-705.5 - Abstract
Summary: 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.
- Published
- 2023
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