Fragment C of Tetanus Toxin: New Insights into Its Neuronal Signaling Pathway

International Journal of Molecular Sciences

Ana C. Calvo¹  Sara Oliván¹  Raquel Manzano¹  Pilar Zaragoza¹  José Aguilera² 

[1] 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; E-Mails:;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; E-Mail:

关键词: clathrin-mediated pathway;    dynamin;    fragment C;    tetanus toxin;    neurotrophin;    Trk receptors;   

DOI  :  10.3390/ijms13066883

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.