Bt Research 2024, Vol.15, No.1, 42-52 http://microbescipublisher.com/index.php/bt 50 mechanisms of receptor expression, such as the role of FOXA in upregulating ABCC2 and ABCC3, can provide new strategies for enhancing the efficacy of Bt toxins. Finally, the potential application of Bt toxins in targeting human cancer cells, as seen with parasporins, opens new avenues for biomedical research. Future studies should focus on several key areas. There is a need to further characterize the structural determinants and binding epitopes involved in Cry toxin-receptor interactions across different insect species. Research should explore the potential for engineering Bt toxins with modified binding specificities to target a broader range of insect pests or to overcome existing resistance mechanisms. Studies should investigate the signaling pathways activated by toxin-receptor interactions to better understand the mechanisms of cytotoxicity and resistance. Additionally, the development of cell-based systems expressing various Bt toxin receptors can provide valuable models for studying the cytotoxic effects and mechanisms of action of different Cry toxins. Interdisciplinary approaches combining structural biology, molecular genetics, and bioinformatics can accelerate the discovery of new targets and the design of next-generation Bt toxins. Acknowledgments We would like to express our sincere gratitude to the two reviewers for their valuable suggestions on this paper. Conflict of Interest Disclosure The authors affirm that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. References Adegawa S., Nakama Y., Endo H., Shinkawa N., Kikuta S., and Sato R, 2017, The domain II loops of Bacillus thuringiensis Cry1Aa form an overlapping interaction site for two Bombyx mori larvae functional receptors ABC transporter C2 and cadherin-like receptor, Biochimica et biophysica acta, Proteins and Proteomics, 1865(2): 220-231. https://doi.org/10.1016/j.bbapap.2016.11.011 Badran A., Guzov V., Huai Q., Kemp M., Vishwanath P., Kain W., Nance A., Evdokimov A., Moshiri F., Turner K., Wang P., Malvar T., and Liu D, 2016, Continuous evolution of B thuringiensis toxins overcomes insect resistance, Nature, 533: 58-63. https://doi.org/10.1038/nature17938 Bravo A., Likitvivatanavong S., Gill S., and Soberón M., 2011, Bacillus thuringiensis: A story of a successful bioinsecticide, Insect Biochemistry and Molecular Biology, 41(7): 423-431. https://doi.org/10.1016/j.ibmb.2011.02.006 Bretschneider A., Heckel D., and Pauchet Y, 2016, Three toxins two receptors one mechanism: mode of action of Cry1A toxins fromBacillus thuringiensis in Heliothis virescens, Insect Biochemistry and Molecular Biology, 76: 109-117. https://doi.org/10.1016/j.ibmb.2016.07.008 Carrière Y., Crickmore N., and Tabashnik B, 2015, Optimizing pyramided transgenic Bt crops for sustainable pest management, Nature Biotechnology, 33: 161-168. https://doi.org/10.1038/nbt.3099 Carrière Y., Crowder D., and Tabashnik B, 2010, Evolutionary ecology of insect adaptation to Bt crops, Evolutionary Applications, 3: 561-573. https://doi.org/10.1111/j.1752-4571.2010.00129.x Chen D., Moar W., Jerga A., Gowda A., Milligan J., Bretsynder E., Rydel T., Baum J., Semeão A., Fu X., Guzov V., Gabbert K., Head G., and Haas J, 2021, Bacillus thuringiensis chimeric proteins Cry1A.2 and Cry1B.2 to control soybean lepidopteran pests: New domain combinations enhance insecticidal spectrum of activity and novel receptor contributions, PLoS ONE, 16. https://doi.org/10.1371/journal.pone.0249150 Chen Z., He F., Xiao Y., Liu C., Li J., Yang Y., Ai H., Peng J., Hong H., and Liu K, 2015, Endogenous expression of a Bt toxin receptor in the Cry1Ac-susceptible insect cell line and its synergistic effect with cadherin on cytotoxicity of activated Cry1Ac, Insect Biochemistry and Molecular Biology, 59: 1-17. https://doi.org/10.1016/j.ibmb.2015.01.014 Domínguez-Arrizabalaga M., Villanueva M., Escriche B., Ancín-Azpilicueta C., and Caballero P, 2020, Insecticidal activity of Bacillus thuringiensis proteins against coleopteran pests, Toxins, 12. https://doi.org/10.3390/toxins12070430 Dutta T., Santhoshkumar K., Veeresh A., Waghmare C., Mathur C., and Sreevathsa R, 2023, RNAi-based knockdown of candidate gut receptor genes altered the susceptibility of Spodoptera frugiperda and S.litura larvae to a chimeric toxin Cry1AcF, PeerJ, 11. https://doi.org/10.7717/peerj.14716
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