C3 exoenzymes, novel insights into structure and action of Rho-ADP-ribosylating toxins

Abstract

The family of C3-like exoenzymes comprises seven bacterial ADP-ribosyltransferases of different origin. The common hallmark of these exoenzymes is the selective N-ADP-ribosylation of the low molecular mass GTPbinding proteins RhoA, B, and C and inhibition of signal pathways controlled by Rho GTPases. Therefore, C3-like exoenzymes were applied as pharmacological tools for analyses of cellular functions of Rho protein in numerous studies. Recent structural and functional analyses of C3-like exoenzymes provide detailed information on the molecular mechanisms and functional consequences of ADP-ribosylation catalyzed by these toxins. More recently additional non-enzymatic actions of C3-like ADP-ribosyltransferases have been identified showing that C3 transferases from Clostridium botulinum and Clostridium limosum form a GDI-like complex with the Ras-like low molecular mass GTPase Ral without ADP-ribosylation. These results add novel information on the molecular mode of action(s) of C3-like exoenzymes and are discussed in this review.

Rho/ROCK pathway is essential to the expansion, differentiation, and morphological rearrangements of human neural stem/progenitor cells induced by lysophosphatidic acid

“…In all cell lines, the effect of LPA on sphere formation was abolished by pretreatment with either the specifi c Rho inhibitor C3 exoenzyme ( 50 ) ( Figs. 2G and 3C, H ) or with the p160 ROCK inhibitor Y27632 used at a dose specifi c to p160ROCK inhibition ( 51 ) ( Figs.…”

Arp2/3-independent assembly of actin by Vibrio type III effector VopL

“…9). We also analyzed the ability of VopL to induce the formation of stress fibers in the presence of Clostridium C3 exoenzyme (C3), which potently inactivates RhoA, RhoB, and RhoC by ADP-ribosylating an asparagine residue located adjacent to the switch I region (27,28). Cells expressing C3 alone lack stress fibers and have only weak actin staining at the cell periphery.…”

C3 peptide enhances recovery from spinal cord injury by improved regenerative growth of descending fiber tracts

“…Since their discovery over 20 years ago bacterial C3 transferases have been used to study the function of Rho proteins in virtually all cellular systems of eukaryotic origin (Aktories and Just, 2005;Vogelsgesang et al, 2007). C3-family proteins have been proven to foster neurite outgrowth and regeneration in a variety of in vitro and in vivo systems (Jin and Strittmatter, 1997;Lehmann et al, 1999;Fischer et al, 2004;Bertrand et al, 2005;Bertrand et al, 2007).…”