GlyCosmos Portal

Submissions

Toxicity of botulinum toxin type A (botA)

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-5250968

PubChem

R-HSA-5250968

Description

Botulinum toxin type A (botA, also known as BoNT/A), a disulfide bonded heavy chain (HC) - light chain (LC) heterodimer ("dichain"), enters the gut typically as a result of consuming contaminated food (Hatheway 1995), as a complex with nontoxic nonhemagglutinin protein (NTNHA, encoded by the C. botulinum ntnha gene) and multiple copies of three hemagglutinin proteins (HA, encoded by the C. botulinum ha17, ha34, and ha70 genes) (Lee et al. 2013). The complex protects the toxin from degradation in the gut and mediates its association with the gut epithelium and transcytosis to enter the circulation. Recent studies in vitro raise the possibility that the toxin may also directly disrupt the basolateral membrane of the gut epithelium (Fujinaga et al. 2013). Circulating toxin molecules associate with gangliosides and synaptic vesicle protein 2 (SV2) exposed by exocytosis at a synapse of a target neuron in the neuromuscular junction (Yowler & Schengrund 2004; Dong et al. 2006). Vesicle recycling brings the toxin into the neuron where the vesicle is acidified (Sudhoff 2004). The lowered pH induces a conformational change in the toxin: its HC forms a passage in the vesicle membrane through which its LC is extruded into the neuronal cytosol and released by reduction of the HC - LC disulfide bond (Montal 2010). The cytosolic LC then catalyzes the cleavage of synaptosomal associated protein 25 (SNAP25) on the cytosolic face of the neuronal plasma membrane (Binz et al. 1994; Schiavo et al. 1993), thereby inhibiting synaptic vesicle fusion with the plasma membrane and exocytosis.

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying **all 4** entries
UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
P60880	Synaptosomal-associated protein 25	SNAP SNAP25	view
Q496J9	Synaptic vesicle glycoprotein 2C	KIAA1054 SV2C	view
Q7L0J3	Synaptic vesicle glycoprotein 2A	KIAA0736 PSEC0174 SV2A	view
Q7L1I2	Synaptic vesicle glycoprotein 2B	KIAA0735 SV2B	view

Displaying **all 2** entries
GlyCosmos Lectin	UniProt ID	Lectin Name	Pathway Viewer
GL_002213	Q45878	HA-17	view
GL_002335	P0DPI0	Botulinum neurotoxin type A	view

If you want to check the location of a particular molecule, you can do so by clicking on the "Switching Highlight" button on the page you have navigated to by clicking on "view".

About Release Notes Help Feedback