title: Involvement of the Tyro3 receptor and its intracellular partner Fyn signaling in Schwann cell myelination.
abstract: During early development of the peripheral nervous system, Schwann cell precursors proliferate, migrate, and differentiate into premyelinating Schwann cells. After birth, Schwann cells envelop neuronal axons with myelin sheaths. Although some molecular mechanisms underlying myelination by Schwann cells have been identified, the whole picture remains unclear. Here we show that signaling through Tyro3 receptor tyrosine kinase and its binding partner, Fyn nonreceptor cytoplasmic tyrosine kinase, is involved in myelination by Schwann cells. Impaired formation of myelin segments is observed in Schwann cell neuronal cultures established from Tyro3-knockout mouse dorsal root ganglia (DRG). Indeed, Tyro3-knockout mice exhibit reduced myelin thickness. By affinity chromatography, Fyn was identified as the binding partner of the Tyro3 intracellular domain, and activity of Fyn is down-regulated in Tyro3-knockout mice, suggesting that Tyro3, acting through Fyn, regulates myelination. Ablating Fyn in mice results in reduced myelin thickness. Decreased myelin formation is observed in cultures established from Fyn-knockout mouse DRG. Furthermore, decreased kinase activity levels and altered expression of myelination-associated transcription factors are observed in these knockout mice. These results suggest the involvement of Tyro3 receptor and its binding partner Fyn in Schwann cell myelination. This constitutes a newly recognized receptor-linked signaling mechanism that can control Schwann cell myelination.
authors.affiliation: Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Torii
authors.affiliation: Department of Systems BioMedicine, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Takada
authors.affiliation: Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Ohno
authors.affiliation: Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan.
authors.forename: Yurika
authors.initials: Y
authors.lastname: Saitoh
authors.affiliation: Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Research Center, Nissei Bilis, Koga, Shiga 528-0052, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Ito
authors.affiliation: Department of Rehabilitation for the Movement Functions, National Rehabilitation Center for Persons with Disabilities Research Institute, Tokorozawa, Saitama 359-8555, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Ogata
authors.affiliation: Graduate School of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Terada
authors.affiliation: Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
authors.forename: Akito
authors.initials: A
authors.lastname: Tanoue
authors.affiliation: Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo 113-8510, Japan yamauchi-j@ncchd.go.jp).
authors.forename: Junji
authors.initials: J
authors.lastname: Yamauchi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism*; D009441:Neurilemma / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D012583:Schwann Cells / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D020794:Receptor Protein-Tyrosine Kinases; C513478:Tyro3 protein, mouse; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn