The actin and Rho-modifying toxins PTC3 and PTC5 of Photorhabdus luminescens: enzyme characterization and induction of MAL/SRF-dependent transcription

22.10.2014

Pfaumann V, Lang AE, Schwan C, Schmidt G, Aktories K.

Cell Microbiol. 2015;17(4):579-594.

Cell Microbiol.          online article

PTC3 and PTC5 are tripartite Tc (toxin complex) toxins from Photorhabdus luminescens, which consist of the binding component TcdA1, the linker component TcdB2 and the enzyme components TccC3 and TccC5, respectively. While PTC5 ADP-ribosylates Rho proteins at Gln61/63 resulting in constitutive activation of the GTPases, PTC3 ADP-ribosylates actin at Thr148 thereby inducing actin polymerization. Here, we identified amino acids involved in ADP-ribosyltransferase activity of TccC3 and TccC5 and analyzed the substrate specificity of Rho-activating TccC5. We compared the time-dependency of Rho protein activation by PTC5 in HeLa cells with the effects of Escherichia coli cytotoxic necrotizing factor 1 (CNF1), which activates Rho GTPases by deamidation of Gln61/63. Using a luciferase reporter assay, we show that PTC5 and PTC3 stimulated gene transcription via myocardin-related transcription factor A (also called MAL) and AP1. MAL activation by PTC5 involved Rho kinase and formins. Activation of AP1 by PTC5 occurred via two MAP kinase pathways involving ERK and Jun kinase, respectively.