The clostridium neurotoxins (CNTs) are metalloporteinases that enter the cytosol and very specifically modifies protein components of the neuroexocytosis apparatus. The aims of the present project are: a- The study of CNTs binding to the presynaptic membrane at nerve terminal, and the consistence with the tyrosine kinase receptors as candidates to be the specific CNTs receptors. b- The study of the CNTs internalization inside some endocytic vesicles, which is postulated thar are acidified by vacuolar ATPase proton pump. c- The study of the neurotoxins translocation from the vesicular lumen to the cytosol. Tetanus toxin, to reach their sites of action in the spinal cord or in the encephalic structures, must be transported after the internalization step. d- We will study the specific features of this CNT that allows this retroaxonal transport. e- And finally, among the actions described by tetanus toxin, we will study the mechanisms implicated in inhibition of the serotonin uptake.
|Effective start/end date||1/10/98 → 1/10/01|