TY - JOUR
T1 - A mechanism of cell death involving an adenylyl cyclase/PKA signaling pathway is induced by the Cry1Ab toxin of Bacillus thuringiensis
AU - Zhang, Xuebin
AU - Candas, Mehmet
AU - Griko, Natalya B.
AU - Taussig, Ronald
AU - Bulla, Lee A.
PY - 2006/6/27
Y1 - 2006/6/27
N2 - Many pathogenic organisms and their toxins target host cell receptors, the consequence of which is altered signaling events that lead to aberrant activity or cell death. A significant body of literature describes various molecular and cellular aspects of toxins associated with bacterial invasion, colonization, and host cell disruption. However, there is little information on the molecular and cellular mechanisms associated with the insecticidal action of Bacillus thuringiensis (Bt) Cry toxins. Recently, we reported that the Cry1Ab toxin produced by Bt kills insect cells by activating a Mg2+-dependent cytotoxic event upon binding of the toxin to its receptor BT-R1. Here we show that binding of Cry toxin to BT-R1 provokes cell death by activating a previously undescribed signaling pathway involving stimulation of G protein (Gαs) and adenylyl cyclase, increased cAMP levels, and activation of protein kinase A. Induction of the adenylyl cyclase/protein kinase A pathway is manifested by sequential cytological changes that include membrane blebbing, appearance of ghost nuclei, cell swelling, and lysis. The discovery of a toxin-induced cell death pathway specifically linked to BT-R 1 in insect cells should provide insights into how insects evolve resistance to Bt and into the development of new, safer insecticides.
AB - Many pathogenic organisms and their toxins target host cell receptors, the consequence of which is altered signaling events that lead to aberrant activity or cell death. A significant body of literature describes various molecular and cellular aspects of toxins associated with bacterial invasion, colonization, and host cell disruption. However, there is little information on the molecular and cellular mechanisms associated with the insecticidal action of Bacillus thuringiensis (Bt) Cry toxins. Recently, we reported that the Cry1Ab toxin produced by Bt kills insect cells by activating a Mg2+-dependent cytotoxic event upon binding of the toxin to its receptor BT-R1. Here we show that binding of Cry toxin to BT-R1 provokes cell death by activating a previously undescribed signaling pathway involving stimulation of G protein (Gαs) and adenylyl cyclase, increased cAMP levels, and activation of protein kinase A. Induction of the adenylyl cyclase/protein kinase A pathway is manifested by sequential cytological changes that include membrane blebbing, appearance of ghost nuclei, cell swelling, and lysis. The discovery of a toxin-induced cell death pathway specifically linked to BT-R 1 in insect cells should provide insights into how insects evolve resistance to Bt and into the development of new, safer insecticides.
KW - Cry toxin
KW - Protein kinase a cadherin receptor cAMP
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=33745597608&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33745597608&partnerID=8YFLogxK
U2 - 10.1073/pnas.0604017103
DO - 10.1073/pnas.0604017103
M3 - Article
C2 - 16788061
AN - SCOPUS:33745597608
SN - 0027-8424
VL - 103
SP - 9897
EP - 9902
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 26
ER -