par Sun, Ch;Wacquier, Benjamin ;Aguilar, D;Carayol, N;Denis, Kevin;Boucherie, S;Simsek, C;Erneux, Christophe ;Lehman, A;Enninga, J;Arbibe, L;Sansonetti, Philippe;Dupont, Geneviève ;Combettes, Laurent;Tran van Nhieu, Guy
Référence EMBO journal, 36, 17, page (2567-2580)
Publication Publié, 2017
Référence EMBO journal, 36, 17, page (2567-2580)
Publication Publié, 2017
Article révisé par les pairs
Résumé : | The role of second messengers in the diversion of cellular processes by pathogens remains poorly studied despite their importance. Among these, Ca2+ virtually regulates all known cell processes, including cytoskeletal reorganization, inflammation, or cell death pathways. Under physiological conditions, cytosolic Ca2+ increases are transient and oscillatory, defining the so-called Ca2+ code that links cell responses to specific Ca2+ oscillatory patterns. During cell invasion, Shigella induces atypical local and global Ca2+ signals. Here, we show that by hydrolyzing phosphatidylinositol-(4,5)bisphosphate, the Shigella type III effector IpgD dampens inositol-(1,4,5)trisphosphate (InsP3) levels. By modifying InsP3 dynamics and diffusion, IpgD favors the elicitation of long-lasting local Ca2+ signals at Shigella invasion sites and converts Shigella-induced global oscillatory responses into erratic responses with atypical dynamics and amplitude. Furthermore, IpgD eventually inhibits InsP3-dependent responses during prolonged infection kinetics. IpgD thus acts as a pathogen regulator of the Ca2+ code implicated in a versatility of cell functions. Consistent with this function, IpgD prevents the Ca2+-dependent activation of calpain, thereby preserving the integrity of cell adhesion structures during the early stages of infection. |