Review Article Open Access
Volume 1 | Issue 4 | DOI: https://doi.org/10.33696/Neurol.1.020

Resolving the Molecular Steps in Clostridial Neurotoxin Light Chain Translocation

  • 1Dalhousie University, Department of Biochemistry and Molecular Biology, Halifax, Nova Scotia, Canada
  • 2Medical College of Wisconsin, 8701 Watertown Plank Road, BSB2 Rm. 2830, Microbiology and Immunology, Milwaukee, WI 53226, USA
+ Affiliations - Affiliations

Corresponding Author

Joseph T. Barbieri, jtb01@mcw.edu 

Received Date: September 02, 2020

Accepted Date: October 13, 2020


The clostridial neurotoxins (CNTs), botulinum toxin and tetanus toxin, are the most toxic proteins for humans. Neurotoxicity is based upon the specificity of the CNTs for neural host receptors and substrates. CNTs are organized into three domains, a Light Chain (LC) that is a metalloprotease and a Heavy Chain (HC) that has two domains, an N-terminal LC translocation domain (HCN) and a C-terminal receptor binding domain (HCC). While catalysis and receptor binding functions of the CNTs have been developed, our understanding of LC translocation is limited. This is due to the intrinsic complexity of the translocation process and limited tools to assess the step-by-step events in LC translocation. Recently, we developed a novel, cell-based TT-reporter to measure LC translocation as the translocation of a β-lactamase reporter across a vesicle membrane in neurons. Using this approach, we identified a role for a cis-Loop, located within the HCN, in LC translocation. In this commentary, we describe our current understanding of how CNTs mediate LC translocation and place the role of the cis-Loop in the LC translocation process relative to other independent functions that have been implicated in LC translocation. Understanding the basis for LC translocation will enhance the use of CNTs in vaccine development and as human therapies.

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