Drk-mediated signaling to Rho kinase is required for anesthesia-resistant memory in Drosophila

Proc Natl Acad Sci U S A. 2017 Oct 10;114(41):10984-10989. doi: 10.1073/pnas.1704835114. Epub 2017 Sep 25.


Anesthesia-resistant memory (ARM) was described decades ago, but the mechanisms that underlie this protein synthesis-independent form of consolidated memory in Drosophila remain poorly understood. Whether the several signaling molecules, receptors, and synaptic proteins currently implicated in ARM operate in one or more pathways and how they function in the process remain unclear. We present evidence that Drk, the Drosophila ortholog of the adaptor protein Grb2, is essential for ARM within adult mushroom body neurons. Significantly, Drk signals engage the Rho kinase Drok, implicating dynamic cytoskeletal changes in ARM, and this is supported by reduced F-actin in the mutants and after pharmacological inhibition of Drok. Interestingly, Drk-Drok signaling appears independent of the function of Radish (Rsh), a protein long implicated in ARM, suggesting that the process involves at least two distinct molecular pathways. Based on these results, we propose that signaling pathways involved in structural plasticity likely underlie this form of translation-independent memory.

Keywords: ARM; Drk; Drok; Drosophila; memory.

MeSH terms

  • Actins / metabolism*
  • Anesthetics / administration & dosage*
  • Animals
  • Animals, Genetically Modified / genetics
  • Animals, Genetically Modified / metabolism
  • Cytoskeleton / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / drug effects
  • Drosophila melanogaster / physiology*
  • Drug Resistance
  • Memory / drug effects
  • Memory / physiology*
  • Mushroom Bodies / physiology
  • Signal Transduction
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism*


  • Actins
  • Anesthetics
  • Drosophila Proteins
  • drk protein, Drosophila
  • rho-Associated Kinases