SDF1-Induced Antagonism of Axonal Repulsion Requires Multiple G-Protein Coupled Signaling Components That Work in Parallel

SDF1 reduces the responsiveness of axonal growth cones to repellent guidance cues in a pertussis-toxin-sensitive, cAMP-dependent manner. Here, we show that SDF1's antirepellent effect can be blocked in embryonic chick dorsal root ganglia (DRGs) by expression of peptides or proteins inhibiting either G alpha(i), G alpha(q), or G beta gamma. SDF1 antirepellent activity is also blocked by pharmacological inhibition of PLC, a common effector protein for G alpha(q). We also show that SDF1 antirepellent activity can be mimicked by overexpression of constitutively active G alpha(i), G alpha(q), or G alpha(s). These results suggest a model in which multiple G protein components cooperate to produce the cAMP levels required for SDF1 antirepellent activity.