Lipid microdomains are involved in neurospecific binding and internalisation of clostridial neurotoxins

The neuroparalytic syndromes of tetanus and botulism are caused by tetanus and botulinum neurotoxins, which are produced by bacteria of the genus Clostridia. These neurotoxins are structurally organised in three-domains endowed with different functions: specific interaction with the neuronal surface, membrane translocation and specific cleavage of three key components of the neurotransmitter release apparatus. Despite an identical intracellular activity, tetanus and botulinum neurotoxins are characterised by a differential intraneuronal trafficking, which is likely to be responsible for the different symptoms observed in clinical tetanus and botulism. This review aims to highlight recent discoveries on the recruitment of clostridial neurotoxins (CNTs) to the surface of neurons and neuronally-differentiated cell lines and to discuss their relevance for the internalisation and sorting of these neurotoxins.