Neuroblast Migration and P2Y Receptor Mediated Calcium Signalling Depend on 9-O-Acetyl GD3 Ganglioside

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 postnatal 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.