A sulfatase regulating the migratory potency of oligodendrocyte progenitor cells through tyrosine phosphorylation of β-catenin
A sulfatase regulating the migratory potency of oligodendrocyte progenitor cells through tyrosine phosphorylation of β-catenin
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DOI：
10.1002/jnr.20197
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发表时间：
2004-09-01
影响因子：
4.2
通讯作者：
Miura, M
中科院分区：
文献类型：
--
作者：
Kakinuma, Y;Saito, F;Miura, M
通过使用cDNA减法，我们确定了一个细胞外硫酸酯酶（RsulfFP 1）从大鼠少突胶质细胞祖细胞（OPC）的mRNA表达下调肿瘤坏死因子-α。RsulfFP 1 mRNA在E15大鼠脊髓的底板和腹侧部分特异性表达。RsulfFP 1的表达模式与OPCs重叠，OPCs也位于脑室区的腹侧区域。在这个阶段之后，RsulfFP 1表达减弱，OPC有效地迁移到整个脊髓。通过RsulfFP 1修饰大鼠O2 A细胞建立的细胞系CG-4细胞激活经典Wnt信号传导。此外，在大鼠脊髓切片培养中，通过反义寡核苷酸缺失RsulfFP 1表达导致OPC迁移受损。通过RsulfFP 1修饰细胞导致免疫沉淀的β-连环蛋白的酪氨酸磷酸化增加，这表明由这种硫酸酯酶诱导的细胞外基质的硫酸化可能是导致参与OPCs迁移的Wnt信号传导增加的原因。因此，本研究揭示了硫酸酯酶负责OPCs的迁移并激活调节迁移的细胞内机制。(C)2004 Wiley-Liss，Inc.
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. (C) 2004 Wiley-Liss, Inc.