title: In vivo expression of the Arf6 Guanine-nucleotide exchange factor cytohesin-1 in mice exhibits enhanced myelin thickness in nerves.
abstract: 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.
authors: Molecular Pharmacology Group, Department of Pharmacology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan.
authors: Tomohiro
authors: T
authors: Torii
authors: Yuki
authors: Y
authors: Miyamoto
authors: Naoko
authors: N
authors: Onami
authors: Hideki
authors: H
authors: Tsumura
authors: Noriko
authors: N
authors: Nemoto
authors: Katsumasa
authors: K
authors: Kawahara
authors: Minoru
authors: M
authors: Kato
authors: Jun
authors: J
authors: Kotera
authors: Kazuaki
authors: K
authors: Nakamura
authors: Akito
authors: A
authors: Tanoue
authors: Junji
authors: J
authors: Yamauchi
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D012584:Sciatic Nerve / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D000089982:ADP-Ribosylation Factor 6; D020662:Guanine Nucleotide Exchange Factors; C100723:cytohesin-1; D020727:ADP-Ribosylation Factors; C000715727:Arf6 protein, mouse
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