Ca2 Influx and Tyrosine Kinases Trigger Bordetella Adenylate Cyclase Toxin ACT Endocytosis. Cell Physiology and Expression of the CD11b-CD18 Integrin Major Determinants of the Entry RouteReport as inadecuate




Ca2 Influx and Tyrosine Kinases Trigger Bordetella Adenylate Cyclase Toxin ACT Endocytosis. Cell Physiology and Expression of the CD11b-CD18 Integrin Major Determinants of the Entry Route - Download this document for free, or read online. Document in PDF available to download.

Humans infected with Bordetella pertussis, the whooping cough bacterium, show evidences of impaired host defenses. This pathogenic bacterium produces a unique adenylate cyclase toxin ACT which enters human phagocytes and catalyzes the unregulated formation of cAMP, hampering important bactericidal functions of these immune cells that eventually cause cell death by apoptosis and-or necrosis. Additionally, ACT permeabilizes cells through pore formation in the target cell membrane. Recently, we demonstrated that ACT is internalised into macrophages together with other membrane components, such as the integrin CD11b-CD18 CR3, its receptor in these immune cells, and GM1. The goal of this study was to determine whether ACT uptake is restricted to receptor-bearing macrophages or on the contrary may also take place into cells devoid of receptor and gain more insights on the signalling involved. Here, we show that ACT is rapidly eliminated from the cell membrane of either CR3-positive as negative cells, though through different entry routes, which depends in part, on the target cell physiology and characteristics. ACT-induced Ca2+ influx and activation of non-receptor Tyr kinases into the target cell appear to be common master denominators in the different endocytic strategies activated by this toxin. Very importantly, we show that, upon incubation with ACT, target cells are capable of repairing the cell membrane, which suggests the mounting of an anti-toxin cell repair-response, very likely involving the toxin elimination from the cell surface.



Author: Kepa B. Uribe , César Martín , Aitor Etxebarria, David González-Bullón, Geraxane Gómez-Bilbao, Helena Ostolaza

Source: http://plos.srce.hr/



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