title: Enhanced exocytosis of the receptor BT-R(1) induced by the Cry1Ab toxin of Bacillus thuringiensis directly correlates to the execution of cell death.
abstract: Cry1Ab toxin produced by Bacillus thuringiensis exerts insecticidal action upon binding to BT-R(1), a cadherin receptor localized in the midgut epithelium of the tobacco hornworm Manduca sexta. The univalent binding of toxin to receptor transmits a death signal into the cell and turns on a multi-step signal transduction pathway involving adenylyl cyclase (AC) and protein kinase A (PKA), which drives the biochemical events that culminate in oncotic cell death. Here, we report that cell killing by the Cry1Ab toxin is a dynamic episode in which the toxin promotes exocytotic transport of BT-R(1) from intracellular membrane vesicles to the plasma membrane. The resultant dramatic increase in BT-R(1) displayed on the surface of toxin-treated cells effects the recruitment and concomitant binding of additional toxin monomers which, in turn, amplifies the original signal in a cascade-like manner. Blocking the activation of AC/PKA signal transduction by either EDTA or PKAi inhibits exocytotic trafficking of BT-R(1) and prevents cell death. Moreover, the exocytosis inhibitor Exo1 blocks translocation of receptor and progression of cell death alike. Obviously, movement of BT-R(1) is mediated by toxin-induced signal transduction and amplification of this signaling apparently is critical to the execution of cell death.
authors.affiliation: Biological Targets, Inc., Pilot Point, Texas 76258, USA; Department of Molecular and Cell Biology, University of Texas at Dallas, Richardson, Texas 75083, USA.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Zhang
authors.forename: Natalya B
authors.initials: NB
authors.lastname: Griko
authors.forename: Susan K
authors.initials: SK
authors.lastname: Corona
authors.forename: Lee A
authors.initials: LA
authors.lastname: Bulla
mesh_terms: D000818:Animals; D001413:Bacillus thuringiensis / Q000378:metabolism*; D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins / Q000378:metabolism / Q000633:toxicity*; D001427:Bacterial Toxins / Q000378:metabolism / Q000633:toxicity*; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003603:Cytotoxins / Q000378:metabolism / Q000633:toxicity; D004705:Endocytosis / Q000187:drug effects; D004731:Endotoxins / Q000378:metabolism / Q000633:toxicity*; D005089:Exocytosis / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006460:Hemolysin Proteins / Q000378:metabolism / Q000633:toxicity*; D042541:Intracellular Space / Q000378:metabolism; D018402:Manduca / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D015820:Cadherins; D003603:Cytotoxins; D004731:Endotoxins; D006460:Hemolysin Proteins; D011956:Receptors, Cell Surface; C030956:insecticidal crystal protein, Bacillus Thuringiensis