Interaction of syntenin-1 and the NG2 proteoglycan in migratory oligodendrocyte precursor cells

Interaction of syntenin-1 and the NG2 proteoglycan in migratory oligodendrocyte precursor cells
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DOI:
10.1074/jbc.m706074200
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发表时间:
2008-03-28
影响因子:
4.8
通讯作者:
Trotter, Jacqueline
Trotter, Jacqueline
中科院分区:
生物学2区
文献类型:
--
作者:
Chatterjee, Nivedita;Stegmueller, Judith;Trotter, Jacqueline

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少突胶质细胞前体沿着轴突迁移是髓鞘形成的必要先决条件,但对其潜在机制知之甚少。 NG2 是一种与少突胶质细胞迁移有关的大膜蛋白多糖。在这里,我们展示了一种名为 syntenin-1 的 PDZ 结构域蛋白与 NG2 相互作用,并且 syntenin-1 对于正常的迁移率是必需的。在酵母双杂交筛选中鉴定出的 Syntenin-1 与 NG2 的关联通过两种蛋白在少突胶质细胞前体细胞过程中的共定位以及细胞提取物的免疫共沉淀得到了证实。 Syntenin-1 还在“共加帽”测定中与 NG2 共定位,证明了活少突胶质细胞中两种蛋白的横向关联。 RNA 干扰介导的神经胶质细胞中 syntenin-1 的下调导致体外迁移显着减少,针对 NG2 的多克隆抗体的存在也是如此。因此,syntenin 在少突胶质细胞前体的迁移中发挥作用,我们认为 NG2-syntenin-1 相互作用对此有所贡献。
Migration of oligodendrocyte precursors along axons is a necessary prerequisite for myelination, but little is known about underlying mechanisms. NG2 is a large membrane proteoglycan implicated in oligodendrocyte migration. Here we show that a PDZ domain protein termed syntenin-1 interacts with NG2 and that syntenin-1 is necessary for normal rates of migration. The association of syntenin-1 with NG2, identified in a yeast two-hybrid screen, was confirmed by colocalization of both proteins within processes of oligodendroglial precursor cells and by coimmunoprecipitation from cell extracts. Syntenin-1 also colocalizes with NG2 in "co-capping" assays, demonstrating a lateral association of both proteins in live oligodendrocytes. RNA interference-mediated down-regulation of syntenin-1 in glial cells results in a significant reduction of migration in vitro, as does the presence of polyclonal antibody against NG2. Thus syntenin plays a role in the migration of oligodendroglial precursors, and we suggest that NG2-syntenin-1 interactions contribute to this.