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BT-R3 Receptor Mediates Killing of the Malaria Vector Anopheles gambiae by Bacillus thuringiensis
Researchers at The University of Texas at Dallas (UTD), led by Dr. Lee Bulla, have demonstrated for the first time the selective cytotoxicity of the Bacillus thuringiensis subsp. israelensis Cry4B toxin is mediated by BT-R3. The Cry toxins produced by Bacillus thuringiensis exert their insecticidal activity by binding with high affinity to their cognate cadherin receptors located on the surface of epithelial cells that line the midgut of susceptible insects. In the case of Anopheles gambiae, binding of the Cry4B toxin by BT-R3, in turn, triggers an internal signaling event that turns on a cell death pathway. The novelty of the research done by the UTD scientists is that they were able to establish the direct involvement of the BT-R3 receptor, cloned from Anopheles gambiae, in mediating toxicity of the Cry4B toxin in living cells. This research is reported in an article published in the July 2013 issue of Experimental Biology and Medicine and is a culmination of proteomics, genomics, and bioinformatics strategies developed in the Bulla laboratory. Validation of BT-R3 as a functional receptor for Cry4B exemplifies the power of proteomics, genomics, and bioinformatics to identify target proteins such as the BT-R3 receptor. The process of target selection starts with data mining of archived protein sequences available in various genome and proteome databases, and results in the selection and annotation of candidate proteins based on their potential to mediate insecticidal action. It brings together genome- and proteome-based target identification and target-directed screening for validating the action of insecticidal proteins such as the Cry4B toxin—engineered or otherwise.