A sulfatase regulating the migratory potency of oligodendrocyte progenitor cells through tyrosine phosphorylation of beta-catenin.
By using cDNA subtraction, we identified an extracellular sulfatase (RsulfFP1) from rat oligodendrocyte progenitor cells (OPCs) whose mRNA expression is down-regulated by tumor necrosis factor-alpha. RsulfFP1 mRNA was expressed specifically in the floor plate and the ventral portion of the rat spinal cord at E15. The expression pattern of RsulfFP1 overlapped with the OPCs, which are also located at the ventral region of the ventricular zone. After this stage, RsulfFP1 expression was attenuated, and the OPCs efficiently migrated throughout the spinal cord. The modification of CG-4 cells, a cell line established from rat O2A cells, by RsulfFP1 activated canonical Wnt signaling. Furthermore, the deletion of RsulfFP1 expression by an antisense oligonucleotide caused impairment of OPC migration in rat spinal cord slice culture. Modification of cells by RsulfFP1 resulted in the increased tyrosine phosphorylation of immunoprecipitated beta-catenin, suggesting that sulfation of the extracellular matrix induced by this sulfatase might be responsible for an increase in Wnt signaling that is involved in the migration of OPCs. Thus, the present study revealed that a sulfatase is responsible for the migration of OPCs and activates intracellular mechanisms that regulate migration.
Kakinuma
Yoshihiko
Y
Laboratory for Cell Recovery Mechanisms, Brain Science Institute, RIKEN, Saitama, Japan.
Saito
Fumiji
F
Ohsawa
Shizue
S
Furuichi
Teiichi
T
Miura
Masayuki
M
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D005455:Fluorescent Antibody Technique / Q000379:methods; D015870:Gene Expression / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D053823:Hedgehog Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D066298:In Vitro Techniques; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013116:Spinal Cord / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology; D013429:Sulfatases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism*; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D051792:Basic Helix-Loop-Helix Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D053823:Hedgehog Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D013429:Sulfatases; D015534:Trans-Activators; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D014443:Tyrosine; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; C495270:CTNNB1 protein, human; C495268:Ctnnb1 protein, rat; C405707:OLIG1 protein, human; C498633:Olig1 protein, rat; C460908:sulfatase RsulfFP1, rat