A molecular circuit composed of CPEB-1 and c-Jun controls growth hormone-mediated synaptic plasticity in the mouse hippocampus
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyProgram in Molecular Medicine
Document Type
Journal ArticlePublication Date
2008-08-22Keywords
AnimalsDown-Regulation
Electric Stimulation
Electrophysiology
Growth Hormone
Hippocampus
Humans
Long-Term Potentiation
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Neuronal Plasticity
Protein Biosynthesis
Proteomics
Proto-Oncogene Proteins c-jun
RNA Precursors
RNA, Messenger
Recombinant Proteins
Synapses
Transcription Factors
Transcription, Genetic
mRNA Cleavage and Polyadenylation Factors
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Cytoplasmic polyadenylation element binding protein 1 (CPEB-1) resides at postsynaptic sites in hippocampal neurons in which it controls polyadenylation-induced translation. CPEB-1 knock-out (KO) mice display defects in some forms of synaptic plasticity and hippocampal-dependent memories. To identify CPEB-1-regulated mRNAs, we used proteomics to compare polypeptides in wild-type (WT) and CPEB-1 KO hippocampus. Growth hormone (GH) was reduced in the KO hippocampus, as were the GH signaling molecules phospho-JAK2 and phospho-STAT3. GH mRNA and pre-mRNA were reduced in the KO hippocampus, suggesting that CPEB-1 controls GH transcription. The transcription factor c-Jun, which binds the GH promoter, was also reduced in the KO hippocampus, as was its ability to coimmunoprecipitate chromatin containing the GH promoter. CPEB-1 binds c-Jun 3' untranslated region CPEs in vitro and coimmunoprecipitates c-Jun RNA in vivo. GH induces long-term potentiation (LTP) when applied to hippocampal slices from WT and CPEB-1 KO mice, but the magnitude of LTP induced by GH in KO mice is reduced. Pretreatment with GH did not reverse the LTP deficit observed in KO mice after theta-burst stimulation (TBS). Cordycepin, an inhibitor of polyadenylation, disrupted LTP induced by either GH application or TBS. Finally, GH application to hippocampal slices induced JAK2 phosphorylation in WT but not KO animals. These results indicate that CPEB-1 control of c-Jun mRNA translation regulates GH gene expression and resulting downstream signaling events (e.g., synaptic plasticity) in the mouse hippocampus.Source
J Neurosci. 2008 Aug 20;28(34):8502-9. Link to article on publisher's siteDOI
10.1523/JNEUROSCI.1756-08.2008Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39266PubMed ID
18716208Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1523/JNEUROSCI.1756-08.2008