Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
ASN Neuro. 2012 Sep 11;4(6):357-69. doi: 10.1042/AN20120035.
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 Ca(2+) oscillations. Immunocytochemistry and pharmacological assays indicated that GCPs expressed P2Y(1)Rs (P2Y(1) receptors) and that deletion or blockade of these receptors decreased the migration rate of GCPs and the frequency of Ca(2+) oscillations. The reduction in P2Y(1)-mediated calcium signals seen in Jones-treated and GD3 synthase-null GCPs were paralleled by P2Y(1)R internalization. We conclude that 9acGD3 controls GCP migration by influencing P2Y(1)R cellular distribution and function.
先前的研究表明，神经节苷脂 9acGD3（9-O-乙酰基 GD3）抗体[J-Ab（Jones 抗体）]可减少体外和体内颗粒细胞祖细胞（GCP）的迁移。在这里，我们使用出生后第 6 天（P）的小鼠小脑外植体，研究了 9acGD3 减少 GCP 迁移的机制。我们发现，用 J-Ab 免疫阻断神经节苷脂或缺乏 GD3 合酶可减少体外 GCP 迁移和 Ca（2+）振荡的频率。免疫细胞化学和药理学测定表明，GCP 表达 P2Y（1）受体（P2Y（1）受体），并且这些受体的缺失或阻断可降低 GCP 的迁移率和 Ca（2+）振荡的频率。Jones 处理和 GD3 合酶缺失的 GCP 中观察到的 P2Y（1）介导的钙信号减少与 P2Y（1）R 内化平行。我们的结论是，9acGD3 通过影响 P2Y（1）R 的细胞分布和功能来控制 GCP 的迁移。
