Cell entry of C3 exoenzyme from clostridium botulinum

Abstract

Clostridium botulinum C3 is the prototype of C3-like ADP-ribosyltransferases that selectively ADP-ribosylate the small GTP-binding proteins RhoA/B/C and inhibit their downstream signaling pathways. It is used as pharmacological tool to study cellular Rho functions. In addition, C3bot harbors a transferase-independent activity on neurons to promote axonal and dendritic growth and branching. Many bacterial protein toxins interact specifically with proteins and/or other membrane components at the surface of target cells. Binding enables access to the appropriate cellular compartment so that the knowledge of the receptor allows essential insight into the mechanism of these toxins. Unlike other bacterial protein toxins (such as the clostridial C1 and C2 toxins from C. botulinum), C3 exoenzyme is devoid of a binding and translocation domain, with which toxins usually initiate receptor-mediated endocytosis followed by access to the intact cell. To date, no specific mechanism for internalization of C3 exoenzyme has been identified. Recently, vimentin was identified as membranous C3-binding partner involved in binding and uptake of C3. Although vimentin is not detected in neurons, vimentin is re-expressed after damage in regenerating neurons. Reappearance of vimentin allows C3 to get access to lesioned neurons/axons to exhibit axonotrophic and dentritotrophic effects.