title: Glutamate signals through mGluR2 to control Schwann cell differentiation and proliferation.
abstract: Rapid saltatory nerve conduction is facilitated by myelin structure, which is produced by Schwann cells (SC) in the peripheral nervous system (PNS). Proper development and degeneration/regeneration after injury requires regulated phenotypic changes of SC. We have previously shown that glutamate can induce SC proliferation in culture. Here we show that glutamate signals through metabotropic glutamate receptor 2 (mGluR2) to induce Erk phosphorylation in SC. mGluR2-elicited Erk phosphorylation requires ErbB2/3 receptor tyrosine kinase phosphorylation to limit the signaling cascade that promotes phosphorylation of Erk, but not Akt. We found that Gβγ and Src are involved in subcellular signaling downstream of mGluR2. We also found that glutamate can transform myelinating SC to proliferating SC, while inhibition of mGluR2 signaling can inhibit demyelination of injured nerves in vivo. These data suggest pathophysiological significance of mGluR2 signaling in PNS and its possible therapeutic importance to combat demyelinating disorders including Charcot-Marie-Tooth disease.
authors.affiliation: Department of Peripheral Nervous System Research National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.|Department of Anatomy, School of Medicine, Tokyo Women's Medical University, Tokyo 162-8666, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Saitoh
authors.affiliation: Department of Peripheral Nervous System Research National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Wakatsuki
authors.affiliation: Department of Peripheral Nervous System Research National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Tokunaga
authors.affiliation: Department of Anatomy, School of Medicine, Tokyo Women's Medical University, Tokyo 162-8666, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Fujieda
authors.affiliation: Department of Peripheral Nervous System Research National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Araki
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D018698:Glutamic Acid / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D051379:Mice; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism; D059348:Peripheral Nerve Injuries / Q000235:genetics* / Q000473:pathology; D017933:Peripheral Nervous System / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology; D012584:Sciatic Nerve / Q000293:injuries / Q000473:pathology
chemical_list: D018698:Glutamic Acid; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C524056:Erbb2 protein, mouse