Aerolysin Induces G-protein Activation and Ca2+Release from Intracellular Stores in Human Granulocytes

• DOI: 10.1074/jbc.273.29.18122
• Publication Date: 2002-07-26T15:01:01Z
• Authors: Karl-Heinz Krause; Marc Fivaz; Antoinette Monod; F. Gisou van der ...
• Keywords: Aerolysin

Aerolysin is a pore-forming toxin that plays key role in the pathogenesis of <i>Aeromonas hydrophila</i>infections. In this study, we have analyzed effect aerolysin on human granulocytes (HL-60 cells). Proaerolysin could bind to these cells, was processed into active aerolysin, and led membrane depolarization, indicating are potential targets for toxin. Fura-2 measurements were used analyze cytosolic [Ca²⁺] homeostasis. As expected toxin, addition Ca²⁺influx across plasma membrane. addition, triggered Ca²⁺ release from agonist thapsigargin-sensitive intracellular stores. This independent aerolysin-induced influx occurred two kinetically distinct phases: an initial rapid transient phase second, more sustained, phase. The first, but not second sensitive pertussis Activation toxin-sensitive G-proteins appeared be consequence pore formation, rather than receptor activation through aerolysin-binding, as it: (i) observed with binding competent, insertion-incompetent mutant, (ii) had marked lag time, (iii) also response other bacterial toxins (staphylococcal α-toxin, streptolysin O) which thought different receptors. G-protein stimulated cellular functions, evidenced by chemotaxis. Our results demonstrate target cells signaling involves G-protein-dependent cell