Dataset Information

The Shigella type III effector IpgD recodes Ca²⁺ signals during invasion of epithelial cells.

ABSTRACT: 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.

SUBMITTER: Sun CH

PROVIDER: S-EPMC5579377 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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The Shigella type III effector IpgD recodes Ca2+ signals during invasion of epithelial cells.

Sun Chun Hui CH Wacquier Benjamin B Aguilar Daniel I DI Carayol Nathalie N Denis Kevin K Boucherie Sylviane S Valencia-Gallardo Cesar C Simsek Ceren C Erneux Christophe C Lehman Alexandre A Enninga Jost J Arbibe Laurence L Sansonetti Philippe P Dupont Geneviève G Combettes Laurent L Tran Van Nhieu Guy G

The EMBO journal 20170712 17

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 ...[more]

PMID: 28701483

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Project description:Pancreatic β-cells release insulin upon a rise in blood glucose. The precise mechanisms of stimulus-secretion coupling, and its failure in Diabetes Mellitus Type 2, remain to be elucidated. The consensus model, as well as a class of currently prescribed anti-diabetic drugs, are based around the observation that glucose-evoked ATP production in β-cells leads to closure of cell membrane ATP-gated potassium (KATP) channels, plasma membrane depolarisation, Ca2+ influx, and finally the exocytosis of insulin granules. However, it has been demonstrated by the inactivation of this pathway using genetic and pharmacological means that closure of the KATP channel alone may not be sufficient to explain all β-cell responses to glucose elevation. We have previously proposed that NAADP-evoked Ca2+ release is an important step in stimulus-secretion coupling in pancreatic β-cells. Here we show using total internal reflection fluorescence (TIRF) microscopy that glucose as well as the Ca2+ mobilising messenger nicotinic acid adenine dinucleotide phosphate (NAADP), known to operate in β-cells, lead to highly localised elementary intracellular Ca2+ signals. These were found to be obscured by measurements of global Ca2+ signals and the action of powerful SERCA-based sequestration mechanisms at the endoplasmic reticulum (ER). Building on our previous work demonstrating that NAADP-evoked Ca2+ release is an important step in stimulus-secretion coupling in pancreatic β-cells, we provide here the first demonstration of elementary Ca2+ signals in response to NAADP, whose occurrence was previously suspected. Optical quantal analysis of these events reveals a unitary event amplitude equivalent to that of known elementary Ca2+ signalling events, inositol trisphosphate (IP3) receptor mediated blips, and ryanodine receptor mediated quarks. We propose that a mechanism based on these highly localised intracellular Ca2+ signalling events mediated by NAADP may initially operate in β-cells when they respond to elevations in blood glucose.

Dataset Information

The Shigella type III effector IpgD recodes Ca²⁺ signals during invasion of epithelial cells.

Publications

The <i>Shigella</i> type III effector IpgD recodes Ca<sup>2+</sup> signals during invasion of epithelial cells.

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