Target intelligence / Profile preview

Insect midgut cadherin-like receptor (CAD)

Target
CAD
Molecular classification
Cadherin superfamily, Cell adhesion molecule, Receptor
01

Overview

Insect midgut cadherin-like receptors are transmembrane proteins located on the brush border membrane of the insect midgut, primarily within the orders Lepidoptera, Coleoptera, and Diptera (Gahan et al., 2001, Science). These proteins are members of the cadherin superfamily and typically consist of multiple extracellular cadherin repeats, a single transmembrane domain, and a cytoplasmic tail (Pigott and Ellar, 2007, Microbiology and Molecular Biology Reviews). While their endogenous biological functions include cell-cell adhesion and maintaining the structural integrity of the intestinal epithelium, they are best known as the primary functional receptors for Cry toxins from Bacillus thuringiensis (Bt) (Vachon et al., 2012, Applied and Environmental Microbiology). The interaction between the toxin and the cadherin receptor is a critical step in the Bt mode of action, facilitating toxin oligomerization and subsequent pore formation in the larval midgut (Soberón et al., 2009, Peptides). This pore formation leads to electrolyte imbalance, septicemia, and the eventual death of the insect pest. Consequently, these receptors are central to the efficacy of Bt-based biopesticides and genetically modified crops expressing Bt toxins. Mutations or down-regulation of these cadherin-like receptors are frequently associated with the development of high-level resistance in field populations of agricultural pests (Tabashnik et al., 2013, Nature Biotechnology).

Other names
Bt-R1Cadherin-like proteinCry toxin receptorBacillus thuringiensis toxin receptorBt-R
02

Mechanism of action

Binding of Cry toxins to the cadherin receptor triggers proteolytic cleavage and toxin oligomerization, leading to the formation of a pre-pore complex that inserts into the midgut membrane, causing osmotic lysis and cell death (Soberón et al., 2009, Peptides).

03

Biological functions

Cell-cell adhesionMidgut epithelial integrityReceptor for Bacillus thuringiensis Cry toxinsMidgut development
04

Disease associations

Agricultural pest infestation
05

Safety considerations

Development of high-level insect resistance through receptor mutations (Tabashnik et al., 2013, Nature Biotechnology)Potential toxicity to non-target lepidopteran speciesReduced binding affinity in resistant populations
06

Interacting drugs

Cry1Ac toxin

3 more in the full profile.

07

Biomarkers

Cadherin gene mutations (e.g., r1 alleles) (Gahan et al., 2001, Science)Receptor expression levelsTruncated cadherin protein variants

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