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Jorge A. Pereira,1
João B. Relvas,1,2
The thickness of the myelin sheath that insulates axons is fittedfor optimal nerve conduction velocity. Here, we show that, inSchwann cells, mammalian disks large homolog 1 (Dlg1) interactswith PTEN (phosphatase and tensin homolog deleted on chromosome10) to inhibit axonal stimulation of myelination. This mechanismlimits myelin sheath thickness and prevents overmyelinationin mouse sciatic nerves. Removing this brake results also inmyelin outfoldings and demyelination, characteristics of someperipheral neuropathies. Indeed, the Dlg1 brake is no longerfunctional in a mouse model of Charcot-Marie-Tooth disease.Therefore, negative regulation of myelination appears to beessential for optimization of nerve conduction velocity andmyelin 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.
The CMT4B disease-causing phosphatases Mtmr2 and Mtmr13 localize to the Schwann cell cytoplasm and endomembrane compartments, where they depend upon each other to achieve wild-type levels of protein expression.