Clostridial C3 proteins: recent approaches to improve neuronal growth and regeneration

Bacterial C3 exoenzymes are widely used tools to investigate cellular events influenced by small GTPases of the Rho subfamily. In this respect they have gained increasing interest in addressing questions dealing with the neuronal morphogenic program during development and after lesion of the mature nervous system. Since central neurons display only very limited capacity to re-grow their axons after injury, successful strategies to improve regeneration are much sought-after. For a long time exclusively considered to be Rho-inhibiting exoenzymes, there is now accumulating evidence that C3 proteins of clostridial sources exhibit their often beneficial effects on neurite outgrowth by other means than ADP-ribosylation. The current review will outline previous attempts to foster neuronal cell growth by the use of C3 transferases and highlight the more recent approaches to improve regenerative axon outgrowth using enzyme-deficient C3 preparations.