Neuroblast migration and P2Y(1) receptor mediated calcium signalling depend on 9-O-acetyl GD3 ganglioside.
Neuroblast migration and P2Y(1) receptor mediated calcium signalling depend on 9-O-acetyl GD3 ganglioside.
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DOI：
10.1042/an20120035
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发表时间：
2012-09-11
期刊：
影响因子：
4.7
通讯作者：
Scemes E
中科院分区：
文献类型：
--
作者：
Santiago MF;Scemes E
先前的研究表明，神经节苷脂9acGD3 （9- o -乙酰基GD3）抗体[J-Ab (Jones antibody)]在体外和体内均可减少GCP（颗粒细胞祖细胞）的迁移。我们利用出生后6天小鼠的小脑外体研究了9acGD3减少GCP迁移的机制。我们发现用J-Ab或缺乏GD3合成酶对神经节苷脂进行免疫阻断会降低GCP体外迁移和Ca2+振荡的频率。免疫细胞化学和药理学分析表明，GCPs表达P2Y1Rs （P2Y1受体），这些受体的缺失或阻断降低了GCPs的迁移率和Ca2+振荡的频率。在琼斯处理和GD3合成酶缺失的GCPs中，p2y1介导的钙信号的减少与P2Y1R内化是平行的。我们得出结论，9acGD3通过影响P2Y1R细胞分布和功能来控制GCP迁移。
Previous studies indicated that a ganglioside 9acGD3 (9-O-acetyl GD3) antibody [the J-Ab (Jones antibody)] reduces GCP (granule cell progenitor) migration in vitro and in vivo. We here investigated, using cerebellar explants of post-natal day (P) 6 mice, the mechanism by which 9acGD3 reduces GCP migration. We found that immunoblockade of the ganglioside with the J-Ab or the lack of GD3 synthase reduced GCP in vitro migration and the frequency of Ca2+ oscillations. Immunocytochemistry and pharmacological assays indicated that GCPs expressed P2Y1Rs (P2Y1 receptors) and that deletion or blockade of these receptors decreased the migration rate of GCPs and the frequency of Ca2+ oscillations. The reduction in P2Y1-mediated calcium signals seen in Jones-treated and GD3 synthase-null GCPs were paralleled by P2Y1R internalization. We conclude that 9acGD3 controls GCP migration by influencing P2Y1R cellular distribution and function.