Dynamics of motor nerve terminal remodeling unveiled using SNARE-cleaving botulinum toxins: the extent and duration are dictated by the sites of SNAP-25 truncation.
Nerve sprouts emerge from motor nerve terminals following blockade of exo-endocytosis for more than 3 days by botulinum neurotoxin (BoNT), and form functional synapses, albeit temporary. Upon restoration of synaptic activity to the parent terminal 7 and 90 days after exposure to BoNT/F or A respectively, a concomitant retraction of the outgrowths was observed. BoNT/E caused short-term neuroparalysis, and dramatically accelerated the recovery of BoNT/A-paralyzed muscle by further truncation of SNAP-25 and its replenishment with functional full-length SNARE. The removal of 9 C-terminal residues from SNAP-25 by BoNT/A leads to persistence of the inhibitory product due to the formation of a nonproductive SNARE complex(es) at release sites, whereas deletion of a further 17 amino acids permits replenishment and a speedy recovery.
Centre for Neurobiochemistry, Department of Biological Sciences, Imperial College of Science, Technology and Medicine, London SW7 2AY, UK.
Frédéric A
FA
Meunier
Godfrey
G
Lisk
Dorothea
D
Sesardic
J Oliver
JO
Dolly
D000595:Amino Acid Sequence / Q000187:drug effects / Q000502:physiology; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D005260:Female; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000378:metabolism; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D010243:Paralysis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D050600:SNARE Proteins; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25; D033921:Vesicular Transport Proteins
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D050600:SNARE Proteins; C494209:Snap25 protein, mouse; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D033921:Vesicular Transport Proteins; D019274:Botulinum Toxins, Type A