2. Academic Validation
  3. The ribosome-associated protein RACK1 represses Kir4.1 translation in astrocytes and influences neuronal activity

The ribosome-associated protein RACK1 represses Kir4.1 translation in astrocytes and influences neuronal activity

  • Cell Rep. 2023 Apr 30;42(5):112456. doi: 10.1016/j.celrep.2023.112456.
Marc Oudart 1,  Katia Avila-Gutierrez 1,  Clara Moch 2,  Elena Dossi 1,  Giampaolo Milior 1,  Anne-Cécile Boulay 1,  Mathis Gaudey 1,  Julien Moulard 1,  Bérangère Lombard 3,  Damarys Loew 3,  Alexis-Pierre Bemelmans 4,  Nathalie Rouach 1,  Clément Chapat 2,  Martine Cohen-Salmon 5
Affiliations

Affiliations

  • 1 Center for Interdisciplinary Research in Biology, College de France, CNRS, INSERM, Université PSL, Labex Memolife, Paris, France.
  • 2 Laboratoire de Biochimie, Ecole Polytechnique, CNRS, Université Paris-Saclay, Palaiseau, France.
  • 3 CurieCoreTech Spectrométrie de Masse Protéomique, Institut Curie, University PSL, Paris, France.
  • 4 CEA, Institut de Biologie François Jacob, Molecular Imaging Research Center (MIRCen), CNRS, Université Paris-Sud, Université Paris-Saclay, Fontenay-aux-Roses, France.
  • 5 Center for Interdisciplinary Research in Biology, College de France, CNRS, INSERM, Université PSL, Labex Memolife, Paris, France. Electronic address: [email protected].
PMID: 37126448 DOI: 10.1016/j.celrep.2023.112456
Abstract

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.

Keywords

CP: Neuroscience; K(+)current; Kir4.1; RACK1; astrocytes; neuroglial interactions; neurotransmission; ribosome; translation.

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