Botulinum Toxin Type A Targets RhoB to Inhibit Lysophosphatidic Acid- Stimulated Actin Reorganization and Acetylcholine Release in PC12 Cells: A Possible Mechanism For Intervention

摘要

We showed that the G-protein activator lysophosphatidic acid (LPA) triggered actin reorganization followed by ACh release in nerve growth factor treated PC12 cells, and that BoNT/A blocked both events through degradation of RhoB by the proteasome. Overexpression of wild-type RhoB caused to overcome toxin s inhibitory effect on actin reorganization/exocytosis stimulated by LPA. A knockdown of the RhoB gene via targeted siRNA transfection resulted in total inhibition of both actin reorganization and ACh release induced by LPA. We conclude that the RhoB signaling pathway regulates ACh release via actin cytoskeletal reorganization, and that botulinum toxin inhibits neuroexocytosis by targeting RhoB pathway.