Localization of the RNA-binding proteins Staufen1 and Staufen2 at the mammalian neuromuscular junction

Authors

  • Guy Bélanger,

    1. Department of Cellular and Molecular Medicine, and Center for Neuromuscular Disease, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
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  • Mark A. Stocksley,

    1. Department of Cellular and Molecular Medicine, and Center for Neuromuscular Disease, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
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  • Marie Vandromme,

    1. Laboratoire de Biologie Moléculaire et Cellulaire, Ecole Normale Supérieure (ENS) Lyon, Unité Médicale de Recherche (UMR) 5663, Lyon, France
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  • Laurent Schaeffer,

    1. Laboratoire de Biologie Moléculaire et Cellulaire, Ecole Normale Supérieure (ENS) Lyon, Unité Médicale de Recherche (UMR) 5663, Lyon, France
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  • Luc Furic,

    1. Département de Biochimie and Centre de Recherche en Sciences Neurologiques, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
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  • Luc DesGroseillers,

    1. Département de Biochimie and Centre de Recherche en Sciences Neurologiques, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
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  • Bernard J. Jasmin

    1. Department of Cellular and Molecular Medicine, and Center for Neuromuscular Disease, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
    2. Ottawa Health Research Institute, Program in Molecular Medicine, Ottawa Hospital, Ottawa, Ontario, Canada
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Address correspondence and reprint requests to Dr Bernard J. Jasmin, Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5. E-mail: jasmin@uottawa.ca

Abstract

Staufen is an RNA-binding protein, first identified for its role in oogenesis and CNS development in Drosophila. Two mammalian homologs of Staufen have been identified and shown to bind double-stranded RNA and tubulin, and to function in the somatodendritic transport of mRNA in neurons. Here, we examined whether Staufen proteins are expressed in skeletal muscle in relation to the neuromuscular junction. Immunofluorescence experiments revealed that Staufen1 (Stau1) and Staufen2 (Stau2) accumulate preferentially within the postsynaptic sarcoplasm of muscle fibers as well as at newly formed ectopic synapses. Western blot analyses showed that the levels of Stau1 and Stau2 are greater in slow muscles than in fast-twitch muscles. Muscle denervation induced a significant increase in the expression of Stau1 and Stau2 in the extrasynaptic compartment of both fast and slow muscles. Consistent with these observations, we also demonstrated that expression of Stau1 and Stau2 is increased during myogenic differentiation and that treatment of myotubes with agrin and neuregulin induces a further increase in the expression of both Staufen proteins. We propose that Stau1 and Stau2 are key components of the postsynaptic apparatus in muscle, and that they contribute to the maturation and plasticity of the neuromuscular junction.

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