A kinase-dependent feedforward loop affects CREBB stability and long term memory formation

Elife. 2018 Feb 23;7:e33007. doi: 10.7554/eLife.33007.


In Drosophila, long-term memory (LTM) requires the cAMP-dependent transcription factor CREBB, expressed in the mushroom bodies (MB) and phosphorylated by PKA. To identify other kinases required for memory formation, we integrated Trojan exons encoding T2A-GAL4 into genes encoding putative kinases and selected for genes expressed in MB. These lines were screened for learning/memory deficits using UAS-RNAi knockdown based on an olfactory aversive conditioning assay. We identified a novel, conserved kinase, Meng-Po (MP, CG11221, SBK1 in human), the loss of which severely affects 3 hr memory and 24 hr LTM, but not learning. Remarkably, memory is lost upon removal of the MP protein in adult MB but restored upon its reintroduction. Overexpression of MP in MB significantly increases LTM in wild-type flies showing that MP is a limiting factor for LTM. We show that PKA phosphorylates MP and that both proteins synergize in a feedforward loop to control CREBB levels and LTM. key words: Drosophila, Mushroom bodies, SBK1, deGradFP, T2A-GAL4, MiMIC.

Keywords: D. melanogaster; Drosophila; MiMIC; SBK1; T2A-GAL4; deGradFP; mushroom bodies; neuroscience.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Conditioning, Classical
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Drosophila / physiology*
  • Drosophila Proteins / metabolism*
  • Gene Knockdown Techniques
  • Genetic Complementation Test
  • Memory, Long-Term*
  • Olfactory Perception
  • Protein Kinases / metabolism*
  • Trans-Activators / metabolism*


  • CrebB protein, Drosophila
  • Cyclic AMP Response Element-Binding Protein
  • Drosophila Proteins
  • Trans-Activators
  • Protein Kinases
  • meng protein, Drosophila
  • Cyclic AMP-Dependent Protein Kinases