Identification of a critical region in the Drosophila ryanodine receptor that confers sensitivity to diamide insecticides

Insect Biochem Mol Biol. 2013 Sep;43(9):820-8. doi: 10.1016/j.ibmb.2013.06.006. Epub 2013 Jun 25.


Anthranilic diamides, which include the new commercial insecticide, chlorantraniliprole, are an exciting new class of chemistry that target insect ryanodine receptors. These receptors regulate release of stored intracellular calcium and play a critical role in muscle contraction. As with insects, nematodes express ryanodine receptors and are sensitive to the plant alkaloid, ryanodine. However the plant parasitic nematode, Meloidogyne incognita, is insensitive to anthranilic diamides. Expression of a full-length Drosophila melanogaster ryanodine receptor in an insect cell line confers sensitivity to the receptor agents, caffeine and ryanodine along with nanomolar sensitivity to anthranilic diamides. Replacement of a 46 amino acid segment in a highly divergent region of the Drosophila C-terminus with that from Meloidogyne results in a functional RyR which lack sensitivity to diamide insecticides. These findings indicate that this region is critical to diamide sensitivity in insect ryanodine receptors. Furthermore, this region may contribute to our understanding of the differential selectivity diamides exhibit for insect over mammalian ryanodine receptors.

Keywords: Chlorantraniliprole; Cyantraniliprole; Cyazypyr™; Flubendiamide; Nematode; Rynaxypyr®.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Diamide / toxicity*
  • Drosophila Proteins / chemistry*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / chemistry
  • Drosophila melanogaster / drug effects
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Helminth Proteins / chemistry
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism
  • Insecticides / toxicity*
  • Molecular Sequence Data
  • Ryanodine Receptor Calcium Release Channel / chemistry*
  • Ryanodine Receptor Calcium Release Channel / genetics
  • Ryanodine Receptor Calcium Release Channel / metabolism*
  • Sequence Alignment
  • Tylenchoidea / chemistry
  • Tylenchoidea / drug effects
  • Tylenchoidea / genetics
  • Tylenchoidea / metabolism


  • Drosophila Proteins
  • Helminth Proteins
  • Insecticides
  • Ryanodine Receptor Calcium Release Channel
  • Diamide