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

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

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Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
Laboratory of Molecular Biology, National Institute of Mental Health, National Institutes of Health, Bethesda, United States.
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States.
Program in Developmental Biology, Baylor College of Medicine, Houston, United States.
Department of Neuroscience, Baylor College of Medicine, Houston, United States.
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.


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.


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

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