EPAC null mutation impairs learning and social interactions via aberrant regulation of miR-124 and Zif268 translation.

Abstract:

:EPAC proteins are the guanine nucleotide exchange factors that act as the intracellular receptors for cyclic AMP. Two variants of EPAC genes including EPAC1 and EPAC2 are cloned and are widely expressed throughout the brain. But, their functions in the brain remain unknown. Here, we genetically delete EPAC1 (EPAC1(-/-)), EPAC2 (EPAC2(-/-)), or both EPAC1 and EPAC2 genes (EPAC(-/-)) in the forebrain of mice. We show that EPAC null mutation impairs long-term potentiation (LTP) and that this impairment is paralleled with the severe deficits in spatial learning and social interactions and is mediated in a direct manner by miR-124 transcription and Zif268 translation. Knockdown of miR-124 restores Zif268 and hence reverses all aspects of the EPAC(-/-) phenotypes, whereas expression of miR-124 or knockdown of Zif268 reproduces the effects of EPAC null mutation. Thus, EPAC proteins control miR-124 transcription in the brain for processing spatial learning and social interactions.

journal_name

Neuron

journal_title

Neuron

authors

Yang Y,Shu X,Liu D,Shang Y,Wu Y,Pei L,Xu X,Tian Q,Zhang J,Qian K,Wang YX,Petralia RS,Tu W,Zhu LQ,Wang JZ,Lu Y

doi

10.1016/j.neuron.2012.02.003

subject

Has Abstract

pub_date

2012-02-23 00:00:00

pages

774-88

issue

4

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(12)00128-6

journal_volume

73

pub_type

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