Molecular basis for the insensitivity of the Monarch (Danaus plexippus) to cardiac glycosides

  title={Molecular basis for the insensitivity of the Monarch (Danaus plexippus) to cardiac glycosides},
  author={Ferdinand Holzinger and Christoph Frick and Michael Wink},
  journal={FEBS Letters},
Mediation of cardiac glycoside insensitivity in the monarch butterfly (Danaus plexippus): Role of an amino acid substitution in the ouabain binding site of Na+,K+-ATPase
The Monarch butterfly (Danaus plexippus) sequesters cardiac glycosides (CG) for its chemical defense against predators and the pattern of amino acid substitution differed, indicating that the Monarch has acquired this mutation independently during evolution.
Studies on the cardenolide sequestration in African milkweed butterflies (Danaidae).
Uptake and sequestration of ouabain and other cardiac glycosides inDanaus plexippus (Lepidoptera: Danaidae): Evidence for a carrier-mediated process
Data provide first evidence that ouabain uptake does not proceed by simple diffusion but with the aid of a carrier mechanism, which would explain the differential cardenolide uptake observed in living larvae.
Selective sequestration of cardenolide isomers by two species of Danaus butterflies (Lepidoptera: Nymphalidae: Danainae)
In adults of Danaus plexippus and D. gilippus, jointly raised on Asclepias curassavica (Asclepiadaceae), two host-plant cardenolides were found in significantly different ratios, suggesting a selective sequestration of calactin.
Resolution of the insect ouabain paradox.
The data show that the Na(+),K(+) ATPase, previously thought to be unimportant, may be as vital in insect tissues as in vertebrates, but can be cryptic to conventional pharmacology.
The evolution of cardenolide‐resistant forms of Na+,K+‐ATPase in Danainae butterflies
A population genetic and phylogenetic analysis of monarchs and their close relatives shows that an ancient Q111L substitution occurred prior to the radiation of all Danainae, followed by a second substitution at the same site to valine (V), which arose before the diversification of the Danaus genus.
Alkaloid tolerance in Manduca sexta and phylogenetically related sphingids (Lepidoptera: Sphingidae)
Application of the cytochrome P450 inhibitor SKF 525A (proadifen) reduced the formation of nicotine N-oxide and the rate of alkaloid degradation and an inducible detoxification mechanism appears to be a strategy in Sphingidae that helps them to live on host plants rich in otherwise toxic secondary metabolites.
Molecular studies on the ouabain binding site of the Na+, K+-ATPase in milkweed butterflies
Analysis of the nucleotide sequences revealed that the single point mutation in the ouabain binding domain (AAC-Asn for CAC-His) was present only in Danaus plexippus, but not in the other species investigated.
Quinolizidine and Pyrrolizidine Alkaloid Chemical Ecology – a Mini-Review on Their Similarities and Differences
  • M. Wink
  • Biology, Chemistry
    Journal of chemical ecology
  • 2019
This mini-review summarizes over 40 years of research on quinolizidine (QAs) and pyrrolizidine alkaloids (PAs) to allow deeper insights in the molecular evolution of these two classes of alkaloid in plant-insect interactions.
Relative Selectivity of Plant Cardenolides for Na+/K+-ATPases From the Monarch Butterfly and Non-resistant Insects
This study has found evidence for relative selectivity of individual cardiac glycosides reaching from 4- to 94-fold differences of inhibition between non-adapted Na+/K+-ATPase and D. plexippus-Na+/ K+- ATPase, which suggests a mechanism how plants could target herbivores selectively and thus provides a strong basis for pairwise coevolutionary interactions between plants and herbivorous insects.


Mutation of a cysteine in the first transmembrane segment of Na,K‐ATPase alpha subunit confers ouabain resistance.
It is proposed that an amino acid residue of the first transmembrane segment located deep in the plasma membrane participates in the structure and the function of the ouabain binding site.
Introduction to Ecological Biochemistry
Hormonal interactions between plants and animals illustrate how sophisticated and complex biochemical interrelationships can become, and a chapter on higher-plant-higher-plant interactions makes it clear that secondary compounds of plants may be weapons of offence as well as defence.
Amino-acid sequence of the catalytic subunit of the (Na+ + K+)ATPase deduced from a complementary DNA
A complementary DNA for the catalytic subunit of the sheep kidney sodium / potassium-dependent ATPase is isolated and characterized and is linked to the phosphorylation site by a 60-amino-acid conserved sequence that may be a major channel for energy transduction.
Insect Chemoreceptors, Insect-deterrent Properties of Secondary Compounds, and the Complexity of Allelopathy.
Structure-function relationships in the sodium-potassium ATPase .alpha. subunit: site-directed mutagenesis of glutamine-111 to arginine and asparagine-122 to aspartic acid generates a ouabain-resistant enzyme
Results demonstrate that the presence of arginine and aspartic acid on the amino end and carboxyl end, respectively, of the H1-H2 extracellular domain of the Na,K-ATPase ..cap alpha..1 subunit together is responsible for the ouabain-resistant character of the rat enzyme.
Molecular genetics of Na,K-ATPase.