title: Protein tyrosine phosphatase receptor type z negatively regulates oligodendrocyte differentiation and myelination.
abstract: BACKGROUND
  Fyn tyrosine kinase-mediated down-regulation of Rho activity through activation of p190RhoGAP is crucial for oligodendrocyte differentiation and myelination. Therefore, the loss of function of its counterpart protein tyrosine phosphatase (PTP) may enhance myelination during development and remyelination in demyelinating diseases. To test this hypothesis, we investigated whether Ptprz, a receptor-like PTP (RPTP) expressed abuntantly in oligodendrocyte lineage cells, is involved in this process, because we recently revealed that p190RhoGAP is a physiological substrate for Ptprz.
  
  
  RESULTS
  We found an early onset of the expression of myelin basic protein (MBP), a major protein of the myelin sheath, and early initiation of myelination in vivo during development of the Ptprz-deficient mouse, as compared with the wild-type. In addition, oligodendrocytes appeared earlier in primary cultures from Ptprz-deficient mice than wild-type mice. Furthermore, adult Ptprz-deficient mice were less susceptible to experimental autoimmune encephalomyelitis (EAE) induced by active immunization with myelin/oligodendrocyte glycoprotein (MOG) peptide than were wild-type mice. After EAE was induced, the tyrosine phosphorylation of p190RhoGAP increased significantly, and the EAE-induced loss of MBP was markedly suppressed in the white matter of the spinal cord in Ptprz-deficient mice. Here, the number of T-cells and macrophages/microglia infiltrating into the spinal cord did not differ between the two genotypes after MOG immunization. All these findings strongly support the validity of our hypothesis.
  
  
  CONCLUSIONS
  Ptprz plays a negative role in oligodendrocyte differentiation in early central nervous system (CNS) development and remyelination in demyelinating CNS diseases, through the dephosphorylation of substrates such as p190RhoGAP.
authors.affiliation: Division of Molecular Neurobiology, National Institute for Basic Biology, Aichi, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kuboyama
authors.forename: Akihiro
authors.initials: A
authors.lastname: Fujikawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Masumura
authors.forename: Ryoko
authors.initials: R
authors.lastname: Suzuki
authors.forename: Masahito
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Masaharu
authors.initials: M
authors.lastname: Noda
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism*; D063308:Myelin-Oligodendrocyte Glycoprotein; D009836:Oligodendroglia / Q000166:cytology / Q000201:enzymology* / Q000502:physiology; D010766:Phosphorylation; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism
chemical_list: D063308:Myelin-Oligodendrocyte Glycoprotein; C516896:Ptprz1 protein, mouse; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5