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SH3TC2, a protein mutant in Charcot-Marie-Tooth neuropathy, links peripheral nerve myelination to endosomal recycling

Stendel, Claudia ; Roos, Andreas ; Kleine, Henning ; Arnaud, Estelle ; Özçelik, Murat ; Sidiropoulos, Páris N. M. ; Zenker, Jennifer ; Schüpfer, Fanny ; Lehmann, Ute ; Sobota, Radoslaw M. ; Litchfield, David W. ; Lüscher, Bernhard ; Chrast, Roman ; Suter, Ueli ; Senderek, Jan

In: Brain, 2010, vol. 133, no. 8, p. 2462-2474

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    Titre
    • SH3TC2, a protein mutant in Charcot-Marie-Tooth neuropathy, links peripheral nerve myelination to endosomal recycling
    Auteur
    • Stendel, Claudia. 1 Institute of Cell Biology, Department of Biology, ETH Zürich, Zürich, Switzerland
    • Roos, Andreas. 2 Institute of Human Genetics, RWTH Aachen University, Aachen, Germany
    • Kleine, Henning. 3 Institute of Biochemistry and Molecular Biology, RWTH Aachen University, Aachen, Germany
    • Arnaud, Estelle. 4 Department of Medical Genetics and Service of Medical Genetics, University of Lausanne and Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
    • Özçelik, Murat. 1 Institute of Cell Biology, Department of Biology, ETH Zürich, Zürich, Switzerland
    • Sidiropoulos, Páris N. M.. 1 Institute of Cell Biology, Department of Biology, ETH Zürich, Zürich, Switzerland
    • Zenker, Jennifer. 4 Department of Medical Genetics and Service of Medical Genetics, University of Lausanne and Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
    • Schüpfer, Fanny. 4 Department of Medical Genetics and Service of Medical Genetics, University of Lausanne and Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
    • Lehmann, Ute. 3 Institute of Biochemistry and Molecular Biology, RWTH Aachen University, Aachen, Germany
    • Sobota, Radoslaw M.. 5 Centre for Experimental Bioinformatics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark
    • Litchfield, David W.. 6 Department of Biochemistry, University of Western Ontario, London, Canada
    • Lüscher, Bernhard. 3 Institute of Biochemistry and Molecular Biology, RWTH Aachen University, Aachen, Germany
    • Chrast, Roman. 4 Department of Medical Genetics and Service of Medical Genetics, University of Lausanne and Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
    • Suter, Ueli. 1 Institute of Cell Biology, Department of Biology, ETH Zürich, Zürich, Switzerland
    • Senderek, Jan. 1 Institute of Cell Biology, Department of Biology, ETH Zürich, Zürich, Switzerland
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • Brain, 2010, vol. 133, no. 8, p. 2462-2474. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:298569
    Summary
    Patients with Charcot-Marie-Tooth neuropathy and gene targeting in mice revealed an essential role for the SH3TC2 gene in peripheral nerve myelination. SH3TC2 expression is restricted to Schwann cells in the peripheral nervous system, and the gene product, SH3TC2, localizes to the perinuclear recycling compartment. Here, we show that SH3TC2 interacts with the small guanosine triphosphatase Rab11, which is known to regulate the recycling of internalized membranes and receptors back to the cell surface. Results of protein binding studies and transferrin receptor trafficking are in line with a role of SH3TC2 as a Rab11 effector molecule. Consistent with a function of Rab11 in Schwann cell myelination, SH3TC2 mutations that cause neuropathy disrupt the SH3TC2/Rab11 interaction, and forced expression of dominant negative Rab11 strongly impairs myelin formation in vitro. Our data indicate that the SH3TC2/Rab11 interaction is relevant for peripheral nerve pathophysiology and place endosomal recycling on the list of cellular mechanisms involved in Schwann cell myelination