Botulinum Toxin Type A Targets RhoB to Inhibit Lysophosphatidic Acid-Stimulated Actin Reorganization and Acetylcholine Release in NGF-Treated Differentiated PC12 Cells
Abstract
It is generally accepted that Botulinum toxin cleaves the 25-kDa synaptosomal-associated protein to inhibit acetylcholine release (neuroexocytosis). Since several reports suggest another mechanism, we investigated possibility that inhibition of neuroexocytosis by the toxin occurs through the RhoB signaling which controls actin cytoskeletal organization. We found that the G-protein activator lysophosphatidic acid (LPA) triggers actin reorganization followed by acetylcholine release in PC12 cells, and that botulinum toxin blocks both events through ubiquitin-dependent degradation of PhoB by the proteasome. Overexpression of wild-type RhoB caused actin reorganization and enhanced release of acetylcholine, and overcame the toxin's inhibitory effect on actin reorganization and exocytosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA483082
Entities
People
- Hiroshi Ishida
- Prabhati Ray
- Xieping Zhang
Organizations
- Walter Reed Army Institute of Research