The myelin sheath consists of a unique multiple layer structure that acts as an insulator between neuronal axons to enhance the propagation of the action potential. In neuropathies such as demyelinating or dismyelinating diseases, chronic
demyelination and defective remyelination occur repeatedly, leading to more severe neuropathy. As yet, little is known about the possibility of
drug target-specific medicine for such diseases. In the developing peripheral nervous system (PNS), myelin sheaths form as Schwann cells wrap individual axons. It is thought that the development of a
drug promoting myelination by Schwann cells would provide effective
therapy against peripheral nerve disorders: to test such treatment, genetically modified mice overexpressing the
drug target molecules are needed. We previously identified an Arf6 activator, the
guanine-nucleotide exchange factor cytohesin-1, as the signaling molecule controlling myelination of peripheral axons by Schwann cells; yet, the important issue of whether
cytohesin-1 itself promotes myelin thickness in vivo has remained unclear. Herein, we show that, in mouse PNS nerves, Schwann cell-specific expression of wild-type
cytohesin-1 exhibits enhanced myelin thickness. Downstream activation of Arf6 is also seen in these transgenic mice, revealing the involvement of the
cytohesin-1 and Arf6 signaling unit in promoting myelination. These results suggest that
cytohesin-1 may be a candidate for the basis of a
therapy for
peripheral neuropathies through its enhancement of myelin thickness.