Aedes cadherin mediates the in vivo toxicity of the Cry11Aa toxin to Aedes aegypti

Cadherin plays an important role in the toxicity of Bacillus thuringiensis Cry proteins. We previously cloned a full-length Aedes cadherin from Aedes aegypti larvae and reported this protein binds Cry11Aa toxin from B. thuringiensis subsp. israelensis with high affinity, ≈ 16.7 nM. Based on these results, we investigated if Aedes cadherin is involved in the in vivo toxicity of Cry11Aa toxin to Ae aegypti. We established a mosquito cell line stably expressing the full-length Aedes cadherin and transgenic mosquitoes silencing Aedes cadherin expression. Cells expressing the Aedes cadherin showed increased sensitivity to Cry11Aa toxin. Cry11Aa toxin at 400 nM killed approximately 37% of the cells in 3 h. Likewise, transgenic mosquitoes with silenced Aedes cadherin expression showed increased tolerance to Cry11Aa toxin. Furthermore, cells expressing Aedes cadherin triggered Cry11Aa oligomerization. These results show the Aedes cadherin plays a pivotal role in Cry11Aa toxicity to Ae. aegypti larvae by mediating Cry11Aa oligomerization. However, since high toxicity was not obtained in cadherin expressing cells, an additional receptor may be needed for manifestation of full toxicity. Moreover, cells expressing Aedes cadherin were sensitive to Cry4Aa and Cry11Ba but not Cry4Ba.  However transgenic mosquitoes with silenced Aedes cadherin expression showed no tolerance to Cry4Aa, Cry4Ba, and Cry11Ba toxins. These results suggest that while Aedes cadherin may mediate Cry4Aa and Cry11Ba toxicity, this cadherin but is not main receptor of Cry4Aa, Cry4Ba and Cry11Ba toxin in Ae. aegypti.