Inhibition of calcium release-activated calcium current by Rac/Cdc42-inactivating clostridial cytotoxins in RBL cells

Using large clostridial cytotoxins as tools, the role of Rho GTPases in act ivation of RBL 2H3 hm1 cells was studied. Clostridium difficile toxin B, wh ich glucosylates Rho, Rac, and Cdc42 and Clostridium sordellii lethal toxin , which glucosylates Rac and Cdc42 but not Rho, inhibited the release of he xosaminidase from RBL cells mediated by the high affinity antigen receptor (Fc epsilon RI). Additionally, toxin B and lethal toxin inhibited the intra cellular Ca2+ mobilization induced by Fc epsilon RI-stimulation and thapsig argin, mainly by reducing the influx of extracellular Ca2+. In patch clamp recordings, toxin B and lethal toxin inhibited the calcium release-activate d calcium current by about 45%. Calcium release-activated calcium current, the receptor-stimulated Ca2+ influx, and secretion were inhibited neither b y the Rho-ADP-ribosylating C3-fusion toxin C2IN-C3 nor by the actin-ADP-rib osylating Clostridium botulinum C2 toxin. The data indicate that Rac and Cd c42 but not Rho are not only involved in late exocytosis events but are als o involved in Ca2+ mobilization most likely by regulating the Ca2+ influx t hrough calcium release-activated calcium channels activated via Fc epsilon RI receptor in RBL cells.