The ATP ‐binding cassette transporter subfamily C member 2 in B ombyx mori larvae is a functional receptor for C ry toxins from B acillus thuringiensis

B acillus thuringiensis is the most widely used biopesticide, and its C ry toxin genes are essential transgenes for the generation of insect‐resistant transgenic crops. Recent reports have suggested that ATP ‐binding cassette transporter subfamily  C 2 ( ABCC 2) proteins are implicated in C ry intoxication, and that a single amino acid insertion results in high levels of resistance to C ry1 toxins. However, there is currently no available direct evidence of functional interactions between ABCC 2 and C ry toxins. To address this important knowledge gap, we investigated the role of B ombyx mori ABCC 2 ( B m ABCC 2) or its mutant from a C ry1 A b‐resistant B . mori strain on C ry1 A toxin action. When we expressed B m ABCC 2 ectopically on S f9 cells, it served as a functional receptor, and the single amino acid insertion found in B m ABCC 2 from C ry1Ab‐resistant larvae resulted in lack of susceptibility to C ry1 A b and C ry1 A c. Using the same expression system, we found that B o. mori cadherin‐like receptor ( B t R 175) conferred susceptibility to C ry1 A toxins, albeit to a lower degree than B m ABCC 2. Coexpression of B t R 175 and B m ABCC 2 resulted in the highest cell susceptibility to C ry1 A , C ry1 F , and even the phylogenetically distant C ry8 C a toxin, when compared with expression of either receptor alone. The susceptibility observed in the coexpressing cells and that in B o. mori larvae are likely to be correlated, suggesting that B t R 175 and B m ABCC 2 are important factors determining larval susceptibility. Our study demonstrates, for the first time, C ry toxin receptor functionality for ABCC 2, and highlights the crucial role of this protein and cadherin in the mechanism of action of C ry toxin.