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Fragment C of Tetanus Toxin: New Insights into Its Neuronal Signaling Pathway
LAGENBIO (Laboratory of Genetics and Biochemistry), Faculty of Veterinary-I3A, Aragonese Institute of Health Sciences (IACS), University of Zaragoza, Miguel Servet 177, 50013 Zaragoza, Spain
Institute of Neurosciences, Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona (UAB), Center of Biomedical Research Network in Neurodegenerative Diseases (CIBERNET), 08193, Cerdanyola del Vallès, Spain
* Author to whom correspondence should be addressed.
Received: 28 March 2012; in revised form: 8 May 2012 / Accepted: 23 May 2012 / Published: 7 June 2012
Abstract: When Clostridium tetani was discovered and identified as a Gram-positive anaerobic bacterium of the genus Clostridium, the possibility of turning its toxin into a valuable biological carrier to ameliorate neurodegenerative processes was inconceivable. However, the non-toxic carboxy-terminal fragment of the tetanus toxin heavy chain (fragment C) can be retrogradely transported to the central nervous system; therefore, fragment C has been used as a valuable biological carrier of neurotrophic factors to ameliorate neurodegenerative processes. More recently, the neuroprotective properties of fragment C have also been described in vitro and in vivo, involving the activation of Akt kinase and extracellular signal-regulated kinase (ERK) signaling cascades through neurotrophin tyrosine kinase (Trk) receptors. Although the precise mechanism of the molecular internalization of fragment C in neuronal cells remains unknown, fragment C could be internalized and translocated into the neuronal cytosol through a clathrin-mediated pathway dependent on proteins, such as dynamin and AP-2. In this review, the origins, molecular properties and possible signaling pathways of fragment C are reviewed to understand the biochemical characteristics of its intracellular and synaptic transport.
Keywords: clathrin-mediated pathway; dynamin; fragment C; tetanus toxin; neurotrophin; Trk receptors
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Calvo, A.C.; Oliván, S.; Manzano, R.; Zaragoza, P.; Aguilera, J.; Osta, R. Fragment C of Tetanus Toxin: New Insights into Its Neuronal Signaling Pathway. Int. J. Mol. Sci. 2012, 13, 6883-6901.
Calvo AC, Oliván S, Manzano R, Zaragoza P, Aguilera J, Osta R. Fragment C of Tetanus Toxin: New Insights into Its Neuronal Signaling Pathway. International Journal of Molecular Sciences. 2012; 13(6):6883-6901.
Calvo, Ana C.; Oliván, Sara; Manzano, Raquel; Zaragoza, Pilar; Aguilera, José; Osta, Rosario. 2012. "Fragment C of Tetanus Toxin: New Insights into Its Neuronal Signaling Pathway." Int. J. Mol. Sci. 13, no. 6: 6883-6901.