CMT 4B: Dlg1-PTEN Interaction Regulates Myelin Thickness to Prevent Damaging Per

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Dlg1-PTEN Interaction Regulates Myelin Thickness to Prevent Damaging Peripheral

Nerve Overmyelination.

Cotter L, Ozçelik M, C, Pereira JA, Locher V, Baumann R, Relvas JB, Suter

U, Tricaud N.

Institute of Cell Biology, Department of Biology, ETH Zürich, CH-8093 Zürich,

Switzerland.

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 disc

large 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 not functional anymore in a mouse model of

Charcot-Marie-Tooth disease (CMT4B). Therefore, negative regulation of

myelination appears to be essential for optimization of nerve conduction

velocity and myelin maintenance.