Determinació dels receptors proteics de molt alta afinitat de les neurotoxines clostridials: implicació dels receptors en els processos d'internalització per endocitosi, translocació i transport retro

Project Details


The closridium neurotoxins (CNTs) are Zn\super 2+\nosuper dependent metalloproteinases that enter in the cytosol by endocytosis and translocation, and modify very specifically protein components of the neurosecretion apparatus. The aims of the present project are 1) The study of CNTs binding to the presynaptic membrane at nerve terminal, and the consistence of the hypothesis of the tyrosine kinase receptors (TyrKRs) as candidates to be the specific \i high affinity\i0 CNTs receptors. 2) The study of the tetanus (TeTx) and botulinium neurotoxins internalisation, and its coincidence with some TyrKRs and some neurotrophins into endocytic vesicles. 3) To complete the study of the alteration by the CNTs of the transduction mechanisms, with especial attention to the Hc-TeTx fragment, responsible of the membrane receptor binding. 4) The study of the retroaxonal transport of the Hc-TeTx fragment and the coincidence with the transport of the membrane TyrKRs, such as trkA, trkB, etc...5) To study the differential characteristics between the activation of the transduction mechanisms by the neurotrophins and by TeTx or the Hc-TeTx fragment. 6) Finally, among all the described TeTx actions, by our group, we will point out our interest in the mechanisms involve in blocking the serotonin transport, as well as the possible use of non-toxic fragments as selective serotonin uptake inhibitors (SSRIs) and as inhibitors with high tropism for the CNS.
Effective start/end date28/12/0127/12/04


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