C3 Exoenzyme: Rho-Inactivating Tool in Cell Biology and a Neurotrophic Agent

ABSTRACT

C3 exoenzyme from Clostridium botulinum is the prototype of bacterial ADP-ribosyltransferases, which selectively modifies the Rho isoforms RhoA, RhoB and RhoC by covalent attachment of an ADP-ribose moiety. ADPribosylation results in inactivation of cellular functions of Rho. Because of its highly restricted substrate specificity, C3 is an established tool in cell biology; to this end C3 is applied as a cell-permeable chimeric toxin. C3 is superior to other molecular biology techniques such as siRNA or knock down approaches as RhoA inactivation or knock down is intrinsically associated with RhoB activation except after C3 treatment. RhoA plays an essential role in axonal growth and repair after neuronal injury. For therapeutic purposes cell- permeable C3 is now locally administered to treat spinal cord injury. Recently, it was reported that ADP-ribosyltransferase activity is not essential for the neurotrophic effect of C3 and that a peptidic fragment of C3 acts neurotrophic.

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