Actin-based confinement of calcium responses during Shigella invasion

Abstract

Shigella, the agent of bacillary dysentery, invades epithelial cells by locally inducing actin reorganization. Upon cell invasion, Shigella induces calcium (Ca 2+) signalling, but its role in invasion has remained unclear. Here we show that components involved in inositol 1, 4, 5-trisphosphate (InsP 3) signalling are implicated in Shigella invasion. Although global Ca 2+ responses are dispensable for bacterial invasion, local Ca 2+ responses of unprecedented long duration are associated with invasion sites. Fluorescence recovery after photo-bleaching experiments indicate that diffusion of small solutes is hindered at Shigella-invasion sites and that diffusion hindrance is dependent on bacterially induced actin reorganization. Computational simulations and experimental challenge of the model support the notion that local accumulation of InsP 3 permitted by restricted diffusion and enrichment of InsP 3 receptors account for sustained local Ca 2+ increases at entry sites. Thus, cytoskeletal reorganization through diffusion hindrance shapes the duration of local Ca 2+ signals. © 2013 Macmillan Publishers Limited. All rights reserved.