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Science 328 (5984): 1415-1418

Copyright © 2010 by the American Association for the Advancement of Science

Dlg1-PTEN Interaction Regulates Myelin Thickness to Prevent Damaging Peripheral Nerve Overmyelination

Laurent Cotter,1,* Murat Özçelik,1,*,{dagger} Claire Jacob,1 Jorge A. Pereira,1 Veronica Locher,1 Reto Baumann,1 João B. Relvas,1,2 Ueli Suter,1 Nicolas Tricaud1,{ddagger}

Abstract: The thickness of the myelin sheath that insulates axons is fitted for optimal nerve conduction velocity. Here, we show that, in Schwann cells, mammalian disks large homolog 1 (Dlg1) interacts with PTEN (phosphatase and tensin homolog deleted on chromosome 10) to inhibit axonal stimulation of myelination. This mechanism limits myelin sheath thickness and prevents overmyelination in mouse sciatic nerves. Removing this brake results also in myelin outfoldings and demyelination, characteristics of some peripheral neuropathies. Indeed, the Dlg1 brake is no longer functional in a mouse model of Charcot-Marie-Tooth disease. Therefore, negative regulation of myelination appears to be essential for optimization of nerve conduction velocity and myelin maintenance.

1 Institute of Cell Biology, Department of Biology, Eidgenössische Technische Hochschule (ETH) Zürich, CH-8093 Zürich, Switzerland.
2 Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.

* These authors contributed equally to this work.

{dagger} Present address: McKinsey & Company, Herrengasse 1-3, A-1010 Vienna, Austria.

{ddagger} To whom correspondence should be addressed. E-mail: nicolas.tricaud{at}cell.biol.ethz.ch

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