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激酶依赖性前馈回路影响 CREBB 的稳定性和长期记忆形成。

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

机构信息

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.

出版信息

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

DOI:10.7554/eLife.33007
PMID:29473541
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5825208/
Abstract

In , 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 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, (, , 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 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.

摘要

在果蝇中,长时记忆(LTM)需要 cAMP 依赖性转录因子 CREBB,其在蘑菇体(MB)中表达并被 PKA 磷酸化。为了鉴定其他参与记忆形成的激酶,我们将编码 Trojan 外显子的序列整合到编码假定激酶的基因中,并选择在 MB 中表达的基因。这些品系通过基于嗅觉厌恶条件反射测定的 UAS-RNAi 敲低筛选学习/记忆缺陷。我们鉴定了一种新型的保守激酶, (,, 在人类),其缺失严重影响 3 小时记忆和 24 小时 LTM,但不影响学习。值得注意的是,在成年 MB 中去除 MP 蛋白会导致记忆丧失,但重新引入后会恢复。在野生型果蝇的 MB 中过表达 MP 会显著增加 LTM,表明 是 LTM 的限制因素。我们表明 PKA 磷酸化 MP,并且这两种蛋白质在正反馈回路中协同作用以控制 CREBB 水平和 LTM。关键词:果蝇,蘑菇体,SBK1,deGradFP,T2A-GAL4,MiMIC。

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