Botulinum toxin intoxication requires retrograde transport and membrane translocation at the ER in RenVM neurons.
Elife
; 122024 Aug 28.
Article
em En
| MEDLINE
| ID: mdl-39196607
ABSTRACT
Botulinum neurotoxin A (BoNT/A) is a highly potent proteolytic toxin specific for neurons with numerous clinical and cosmetic uses. After uptake at the synapse, the protein is proposed to translocate from synaptic vesicles to the cytosol through a self-formed channel. Surprisingly, we found that after intoxication proteolysis of a fluorescent reporter occurs in the neuron soma first and then centrifugally in neurites. To investigate the molecular mechanisms at play, we use a genome-wide siRNA screen in genetically engineered neurons and identify over three hundred genes. An organelle-specific split-mNG complementation indicates BoNT/A traffic from the synapse to the soma-localized Golgi in a retromer-dependent fashion. The toxin then moves to the ER and appears to require the Sec61 complex for retro-translocation to the cytosol. Our study identifies genes and trafficking processes hijacked by the toxin, revealing a new pathway mediating BoNT/A cellular toxicity.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transporte Proteico
/
Retículo Endoplasmático
/
Neurônios
Limite:
Animals
Idioma:
En
Revista:
Elife
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Singapura