The ribosome-associated protein RACK1 represses Kir4.1 translation in astrocytes and influences neuronal activity
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,
Martine Cohen-Salmon
Affiliations
Marc Oudart
Center for Interdisciplinary Research in Biology, College de France, CNRS, INSERM, Université PSL, Labex Memolife, Paris, France
Katia Avila-Gutierrez
Center for Interdisciplinary Research in Biology, College de France, CNRS, INSERM, Université PSL, Labex Memolife, Paris, France
Clara Moch
Laboratoire de Biochimie, Ecole Polytechnique, CNRS, Université Paris-Saclay, Palaiseau, France
Elena Dossi
Center for Interdisciplinary Research in Biology, College de France, CNRS, INSERM, Université PSL, Labex Memolife, Paris, France
Giampaolo Milior
Center for Interdisciplinary Research in Biology, College de France, CNRS, INSERM, Université PSL, Labex Memolife, Paris, France
Anne-Cécile Boulay
Center for Interdisciplinary Research in Biology, College de France, CNRS, INSERM, Université PSL, Labex Memolife, Paris, France
Mathis Gaudey
Center for Interdisciplinary Research in Biology, College de France, CNRS, INSERM, Université PSL, Labex Memolife, Paris, France
Julien Moulard
Center for Interdisciplinary Research in Biology, College de France, CNRS, INSERM, Université PSL, Labex Memolife, Paris, France
Bérangère Lombard
CurieCoreTech Spectrométrie de Masse Protéomique, Institut Curie, University PSL, Paris, France
Damarys Loew
CurieCoreTech Spectrométrie de Masse Protéomique, Institut Curie, University PSL, Paris, France
Alexis-Pierre Bemelmans
CEA, Institut de Biologie François Jacob, Molecular Imaging Research Center (MIRCen), CNRS, Université Paris-Sud, Université Paris-Saclay, Fontenay-aux-Roses, France
Nathalie Rouach
Center for Interdisciplinary Research in Biology, College de France, CNRS, INSERM, Université PSL, Labex Memolife, Paris, France
Clément Chapat
Laboratoire de Biochimie, Ecole Polytechnique, CNRS, Université Paris-Saclay, Palaiseau, France
Martine Cohen-Salmon
Center for Interdisciplinary Research in Biology, College de France, CNRS, INSERM, Université PSL, Labex Memolife, Paris, France; Corresponding author
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.
