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

ELife
Pei-Tseng LeeHugo J Bellen

Abstract

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.

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Citations

Sep 24, 2019·Antibodies·Gustavo AguilarMarkus Affolter
Mar 23, 2018·ELife·Pei-Tseng LeeHugo J Bellen
Dec 14, 2018·Genetics·Christoph Heier, Ronald P Kühnlein
Feb 8, 2021·Current Opinion in Cell Biology·Yanfei Jiang, Nan Hao

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Methods Mentioned

BETA
transgenic
gene trap
gene-trap
PCR
pulldown
transfection

Software Mentioned

Synergy
deGradFP
MiMIC
KaleidaGraph

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