title: Roles of meltrin-beta/ADAM19 in progression of Schwann cell differentiation and myelination during sciatic nerve regeneration.
abstract: Remyelination is an important aspect of nerve regeneration after nerve injury, but the underlying mechanisms are not fully understood. Here, we show that meltrin-beta (ADAM19), a member of the ADAM (a disintegrin and metalloprotease) family, plays crucial roles in nerve regeneration after a crush injury to the sciatic nerves. The expression of meltrin-beta was up-regulated in neurons after the crush injury. Morphometrical analysis revealed a delay in remyelination in meltrin-beta-deficient nerves, whereas no significant defects were observed in their axon elongation. The activation of Krox-20, an indispensable transcription factor for myelination, was delayed in meltrin-beta-deficient nerves and was accompanied by the retarded expression of myelin-related proteins. Expression of Krox-20 in Schwann cells was mediated by Akt. Phosphorylation of Akt but not that of Erks was reduced in regenerating nerves of meltrin-beta-deficient mice. The cell membrane fraction prepared from meltrin-beta-deficient nerves showed a defective activation of Akt in the membrane-loaded Schwann cells. Meltrin-beta-deficient mice exhibited delayed sciatic functional recovery after the nerve crush. Altogether, these results reveal a role of meltrin-beta in Schwann cell differentiation and re-myelination in nerve regeneration. Moreover, this study suggests that meltrin-beta functions as a modulator of juxtacrine signaling from axons that activate the Akt pathway and the Krox-20 expression, which is the prerequisite for Schwann cell differentiation.
authors.affiliation: Department of Growth Regulation, Institute for Frontier Medical Sciences, Kyoto University, Kawahara-cho 53, Shogo-in, Kyoto 606-8507, Japan; Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center for Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira 187-8502, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Wakatsuki
authors.affiliation: Department of Growth Regulation, Institute for Frontier Medical Sciences, Kyoto University, Kawahara-cho 53, Shogo-in, Kyoto 606-8507, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Yumoto
authors.affiliation: Department of Growth Regulation, Institute for Frontier Medical Sciences, Kyoto University, Kawahara-cho 53, Shogo-in, Kyoto 606-8507, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Komatsu
authors.affiliation: Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center for Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira 187-8502, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Araki
authors.affiliation: Department of Growth Regulation, Institute for Frontier Medical Sciences, Kyoto University, Kawahara-cho 53, Shogo-in, Kyoto 606-8507, Japan. Electronic address: asehara@frontier.kyoto-u.ac.jp.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Sehara-Fujisawa
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D002454:Cell Differentiation / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000166:cytology*; D012584:Sciatic Nerve / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt; D051722:ADAM Proteins; C096116:Adam19 protein, mouse